Background A residual risk of ischemic events following an acute coronary syndrome ( ACS ) remains despite antiplatelet therapy. The addition of an antithrombin as part of a “dual pathway” approach may further improve outcomes as thrombin generation persists for several months post‐ ACS . The present study evaluates the safety and efficacy of “dual pathway” therapy (rivaroxaban plus aspirin) as compared with aspirin monotherapy among post‐ ACS patients. Methods and Results A total of 1477 patients were analyzed in a pooled analysis of subsets of the ATLAS ACS ‐ TIMI (Anti‐Xa Therapy to Lower cardiovascular events in addition to Aspirin with or without thienopyridine therapy in Subjects with Acute Coronary Syndrome – Thrombolysis in Myocardial Infarction) 46 and ATLAS ACS 2‐ TIMI 51 trials including post‐ ACS patients receiving aspirin monotherapy and randomized to either rivaroxaban 2.5 mg BID or rivaroxaban 5 mg BID or placebo. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction ( MI ), or stroke (ischemic, hemorrhagic, or of uncertain cause). The primary safety end point was TIMI ‐non‐coronary artery bypass ( CABG ) major bleeding. The combined rivaroxaban group (2.5 or 5 mg BID ) among stabilized post‐ ACS patients on a background of aspirin monotherapy was associated with a significant reduction in the primary end point as compared with placebo (hazard ratio=0.65, 95% CI =0.45–0.92, P =0.016). Although the combined rivaroxaban dose groups were associated with higher rates of non‐ CABG TIMI major bleeding, the 2.5 mg dose group was not, and the overall number of patients experiencing a non‐ CABG TIMI major bleeding event was low (1.5%). Conclusions Among patients in the immediate post‐ ACS period, a “dual pathway” approach using aspirin and low‐dose rivaroxaban may reduce the risk of secondary atherothrombotic events, but increase bleeding risk. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 00402597; NCT 00809965.