Dozens of commonly prescribed medications raise your risk of blood clots, from birth control pills and hormone therapy to steroids, certain painkillers, and psychiatric drugs. The risk varies widely depending on the specific medication, the dose, and your personal health profile. Here’s what the evidence shows for each major category.
Birth Control Pills
Combined oral contraceptives (those containing both estrogen and a progestin) are one of the most well-known medication-related causes of blood clots. The incidence is roughly 6 per 10,000 women per year of use. That’s meaningfully higher than the baseline rate for women not on the pill, but still lower than the roughly 20 per 10,000 rate seen during pregnancy and the postpartum period.
Not all pills carry the same risk. Second-generation formulations containing levonorgestrel are consistently linked to lower clot risk than third-generation pills containing newer progestins like desogestrel or gestodene. If you’re concerned about clots and want to stay on hormonal birth control, this is a practical distinction worth discussing with your prescriber. Progestin-only methods (the mini-pill, hormonal IUDs, the implant) do not carry the same elevated risk because they lack the estrogen component.
How Estrogen Promotes Clotting
Estrogen, whether from birth control or hormone replacement therapy, shifts the blood’s chemistry toward clotting. It raises levels of several clotting proteins, including fibrinogen and factors II, VII, IX, X, and XII. At the same time, it lowers antithrombin III, a natural anticoagulant, and reduces protein S, which normally helps keep clotting in check. The net effect is blood that forms clots more easily and breaks them down less efficiently.
This mechanism is why nearly every estrogen-containing medication on this list shares a similar risk profile, and why the delivery method matters so much for hormone therapy.
Hormone Replacement Therapy
For women managing menopause symptoms, the form of estrogen makes a significant difference. Oral estrogen therapy carries about 63% higher risk of a first blood clot compared to transdermal options like patches or gels. The risk of deep vein thrombosis specifically is roughly doubled with oral estrogen versus transdermal. This is because oral estrogen passes through the liver first, where it ramps up production of clotting factors. Transdermal estrogen enters the bloodstream directly and largely bypasses this effect.
If you need hormone therapy and have risk factors for clots (obesity, smoking history, prior clots, or a family history), transdermal delivery is generally the safer route.
Testosterone Therapy
Testosterone replacement therapy raises clot risk in both men with and without clinically low testosterone levels. A large study published in JAMA Internal Medicine found that men with diagnosed low testosterone had about 2.3 times the odds of developing a blood clot while on therapy, while men without that diagnosis had roughly double the odds. For men under 65 without low testosterone, the risk was even more pronounced: nearly three times higher during the three months surrounding a clot event.
The FDA added a warning about blood clots to testosterone product labels in 2014. The risk appears highest in the early months of treatment, so new users should be especially alert to symptoms like leg swelling, pain, or sudden shortness of breath.
Tamoxifen and Cancer Treatments
Tamoxifen, widely prescribed for breast cancer prevention and treatment, increases the risk of blood clots two- to threefold. In one study of 446 patients, 3.4% developed a clot while on the drug. That percentage rises during surgery or prolonged immobility, which is why oncology teams often adjust or pause tamoxifen around surgical procedures.
Other cancer treatments also raise clot risk. Some chemotherapy drugs damage blood vessel walls directly, and certain targeted therapies that block blood vessel growth can disrupt the normal balance between clotting and bleeding. Cancer itself is a major clot risk factor, so distinguishing between the disease and the treatment as the cause can be difficult.
Corticosteroids
Systemic corticosteroids, the kind taken orally or by injection for conditions like asthma, rheumatoid arthritis, or inflammatory bowel disease, roughly double the risk of blood clots during ongoing use. A large population-based study found an adjusted incidence rate ratio of 2.02 for continuing steroid users compared to non-users.
The risk is dose-dependent. Cumulative doses equivalent to more than 1,000 mg of prednisolone were associated with about twice the baseline risk. Lower cumulative doses (under 10 mg equivalent) showed no meaningful increase. Short courses for a sinus infection or poison ivy are unlikely to matter, but long-term use at moderate or high doses is a genuine concern.
Common Painkillers (NSAIDs)
This one surprises most people. Several over-the-counter anti-inflammatory painkillers are associated with increased clot risk. In a large UK study of patients with knee osteoarthritis, current diclofenac users had a 63% higher risk of blood clots, and ibuprofen users had a 49% higher risk compared to people who had stopped using these drugs. Meloxicam and celecoxib showed smaller but still significant increases of 29% and 30%, respectively.
Naproxen was the notable exception. It showed no increased clot risk at all in this study. If you take anti-inflammatory painkillers regularly and have other clot risk factors, this distinction could be relevant to your choice of medication.
Antipsychotic Medications
Second-generation antipsychotics, particularly clozapine and olanzapine, are linked to higher rates of blood clots. These drugs promote clotting through several pathways: they activate receptors on platelets that encourage clumping, trigger inflammation that damages blood vessel walls, and in some cases stimulate antibodies that interfere with normal anticoagulant processes.
Among the atypical antipsychotics, clozapine carries the highest risk, followed by olanzapine and risperidone (which roughly doubles the hospitalization rate for clots). Quetiapine shows a smaller but measurable signal. Aripiprazole appears to carry the lowest risk in this class. These drugs are also associated with weight gain and reduced mobility, both of which independently raise clot risk, compounding the problem.
Red Blood Cell-Stimulating Drugs
Medications that boost red blood cell production, commonly prescribed for anemia in people with kidney disease or those undergoing chemotherapy, increase clot risk by thickening the blood. The danger rises when these drugs push hemoglobin levels to 12 g/dL or higher. At that threshold, the blood becomes viscous enough to significantly increase the chance of clots, heart attacks, strokes, and heart failure. Doses are typically reduced or stopped before reaching that level.
How Personal Risk Factors Multiply the Danger
Medication-related clot risk doesn’t exist in isolation. Obesity alone roughly triples the odds of a blood clot, but when combined with another risk factor like medication use, the odds jump to more than five times normal. Smoking, recent surgery, prolonged immobility, cancer, heart failure, and varicose veins all interact with drug-related risk in similar ways. In one study, obesity combined with at least one additional risk factor in nearly 58% of clot cases.
This stacking effect is why the same medication can be relatively safe for one person and dangerous for another. A healthy-weight, active 25-year-old on birth control pills faces a very different risk profile than a 40-year-old smoker with obesity on the same prescription. If you’re taking any of the medications listed above and you have additional risk factors, that combination is worth a conversation with your prescriber, particularly if you’re about to face a period of immobility from surgery, travel, or illness.