Eliquis (apixaban) and Xarelto (rivaroxaban) are both blood thinners that work by blocking the same clotting protein in your blood, called factor Xa. They’re approved for the same core uses, and both represent a newer generation of anticoagulants that replaced warfarin for many patients. But they differ in meaningful ways: how often you take them, how they interact with food, their relative bleeding risks, and how your body processes them.
How Both Drugs Work
Eliquis and Xarelto belong to the same drug class, known as direct oral anticoagulants (DOACs). Both are small molecules that latch onto the active site of factor Xa, a key enzyme in the chain reaction that forms blood clots. By blocking factor Xa, they reduce your body’s ability to generate thrombin, the protein that ultimately turns liquid blood into a clot. They also block factor Xa when it’s already assembled into a larger clotting complex on the surface of activated platelets, which makes them effective at interrupting clot formation at multiple stages.
Both drugs were approved by the FDA about a decade ago for the same primary uses: preventing stroke in people with atrial fibrillation (AFib) and treating or preventing deep vein thrombosis (DVT) and pulmonary embolism (PE). If you’ve been prescribed one or the other, it was likely for one of these reasons.
Dosing: Once Daily vs. Twice Daily
This is one of the most practical differences between the two drugs. Xarelto is taken once a day at its maintenance dose of 20 mg. Eliquis is taken twice a day, typically 5 mg in the morning and 5 mg in the evening.
For some people, once-daily dosing is simpler and easier to remember. For others, the difference is negligible. But if you miss a dose of Eliquis, the gap in protection is shorter because the next dose is only about 12 hours away, not 24. This can matter for people who occasionally forget a pill.
Both drugs also have a “lead-in” period when first starting treatment for a blood clot. Eliquis starts at 10 mg twice daily before stepping down, while Xarelto starts at 15 mg twice daily before shifting to its once-daily maintenance dose.
Food Requirements
Xarelto at its higher doses (15 mg and 20 mg) needs to be taken with food. Without a meal, your body absorbs significantly less of the drug. Studies show that bioavailability reaches 80% or higher only when these doses are taken with food. At lower doses (10 mg or below), absorption is high regardless of meals.
Eliquis doesn’t have this requirement. You can take it with or without food, which gives you more flexibility in your daily routine.
Bleeding Risk: Where They Diverge Most
Both Eliquis and Xarelto carry a risk of bleeding, as all blood thinners do. But the two drugs are not equal on this front. A large meta-analysis published in Frontiers in Pharmacology, pooling data from 37 randomized controlled trials, found that standard-dose Eliquis (10 mg daily) was associated with a 45% lower risk of major gastrointestinal bleeding compared to standard-dose Xarelto (15 mg or more daily). Even when comparing the same 10 mg dose of each drug, Eliquis still showed a lower GI bleeding risk.
Separately, Xarelto at 10 mg daily was found to significantly increase the risk of major GI bleeding compared to control groups, with an odds ratio of 1.41. This pattern has made Eliquis the preferred choice for many clinicians when GI bleeding is a concern, particularly in older patients or those with a history of stomach or intestinal problems.
In their landmark clinical trials (ARISTOTLE for Eliquis and ROCKET AF for Xarelto), both drugs reduced stroke and intracranial hemorrhage compared to warfarin, and both lowered all-cause mortality. A pooled analysis of over 71,000 patients across all major DOAC trials found that this newer class of blood thinners cut the risk of bleeding inside the brain by roughly half compared to warfarin. However, as a class, they did increase gastrointestinal bleeding slightly.
Kidney Function and Dose Adjustments
Your kidneys play a role in clearing both drugs from your body, so reduced kidney function affects how each one is managed. Both Eliquis and Xarelto should be avoided if kidney filtration drops below 15 mL/min, a level that indicates severe impairment.
Between those extremes, the drugs differ. For people with moderate kidney impairment (filtration between 15 and 29 mL/min), Eliquis can still be used with a dose reduction to 2.5 mg twice daily for AFib patients. It can also be continued with caution for treating blood clots at that kidney function level. Xarelto requires consulting more specific guidance across its different uses when kidney filtration falls below 50 mL/min, and dosing adjustments vary by indication.
This flexibility with kidney function is another reason some doctors lean toward Eliquis for patients with declining kidney health.
What Happens in a Bleeding Emergency
Both drugs share the same reversal agent. Andexanet alfa, approved by the FDA in 2018, works as a decoy: it mimics the shape of factor Xa and soaks up the drug molecules circulating in your blood, preventing them from blocking your real clotting factors. This restores your blood’s ability to clot during life-threatening or uncontrolled bleeding. Before this reversal agent existed, managing serious bleeds on these medications was much more difficult.
Cost and Generic Availability
Both Eliquis and Xarelto are expensive brand-name medications. A generic version of Eliquis (apixaban) has received FDA approval, but the brand-name manufacturer still holds exclusive market rights, so generic versions may not yet be widely available at pharmacies. The timeline for affordable generic competition depends on when those exclusivity rights expire.
Insurance coverage, copay cards from the manufacturers, and your specific plan all affect what you’ll actually pay. If cost is a deciding factor, it’s worth checking your pharmacy’s price for both and comparing any available discount programs.
Which One Is Better for You
Neither drug is universally better. They treat the same conditions, work through the same mechanism, and share a reversal agent. The choice often comes down to a few key tradeoffs. Xarelto’s once-daily dosing is more convenient. Eliquis has a more favorable bleeding profile, especially for GI bleeding. Eliquis offers more flexibility with food and kidney impairment. Both effectively prevent strokes in AFib and treat blood clots.
In practice, many prescribers have shifted toward Eliquis for patients at higher bleeding risk, while Xarelto remains a strong option for people who prioritize simplicity or who do well on once-daily medications. Your kidney function, bleeding history, other medications, and personal preferences all factor into the decision.