Introduction: Antiplatelet therapy with aspirin is a mainstay for secondary prevention of ischemic strokes and other vascular events. Yet, many patients do not take aspirin or discontinue it due to gastrointestinal (GI) side effects. Proton pump inhibitors are often co-prescribed to those who develop aspirin-related dyspepsia or who are at risk for GI complications. We investigated a new aspirin formulation (PA32540), which is a coordinated-delivery tablet of immediate-release (IR) omeprazole (40 mg) and enteric-coated (EC) aspirin (325 mg), in an effort to improve co-prescription compliance, reduce GI side effects, and improve overall antiplatelet therapy efficacy. Methods: Two phase 3 double-blind multicenter studies included a subset of subjects with ≥ 1 transient ischemic attack or ischemic stroke who were prescribed aspirin at 325 mg once daily for ≥ 3 months for secondary prevention of cardiovascular (CV) events. All subjects were randomly assigned to once-daily treatment with PA32540 or 325 mg EC aspirin. Use of coumadin was excluded. Endoscopic assessments for gastric or duodenal ulcers were performed at screening and at 1, 3, and 6 months. Major adverse cardiovascular events (MACE) were adjudicated by an independent blinded endpoint committee. Results: Baseline characteristics and rates of discontinuation are shown in Table 1. The rate of gastroduodenal ulcers and discontinuations due to upper GI events were significantly lower following administration of PA32540 vs EC aspirin alone over 6 months. No difference in MACE was identified. Conclusion: In patients with previous cerebrovascular disease, PA32540 was associated with a significantly lower rate of endoscopic gastroduodenal ulcers, a higher rate of treatment continuation, and no increase in the number of MACE, compared with aspirin alone. These findings support the use of a single tablet prescription of omeprazole and aspirin for improving the overall efficacy of antiplatelet therapy.