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Background: Low-dose aspirin lowers cardiovascular event risk; dual-pathway inhibition (DPI) using low-dose aspirin with low-dose rivaroxaban may reduce this risk further. A systematic literature review and meta-analysis compared the efficacy, safety and net clinical benefit (NCB) of DPI with aspirin., Methods: PubMed and Embase were searched for randomised controlled trials reporting clinical efficacy, safety and NCB of DPI compared with aspirin alone in patients with coronary artery disease (CAD) and/or peripheral artery disease. Six articles representing four trials were included., Results: DPI versus aspirin alone significantly reduced major adverse cardiovascular events (HR 0.77; 95% CI [0.69-0.87]; p<0.01), increased International Society on Thrombosis and Haemostasis major bleeding events (HR 1.67; 95% CI [1.37-2.02]; p<0.01) and resulted in a significant NCB (HR 0.79; 95% CI [0.70-0.90]; p<0.01)., Conclusion: These results underscore the potential benefit of DPI in patients with CAD, including those in the immediate post-acute coronary syndrome stage and with established CAD, as well as patients with peripheral artery disease., Competing Interests: Disclosure: DS, MJB, ALC, AL, FS, OS and ZS are members of the Bayer AG global advisory board. DS has received consulting fees and payments from Bayer, Sanofi and Daiichi, and is on the ESC Taskforce. FS has received honoraria for presentations from Bayer; expenses paid by Eli Lilly and Bayer, and is on the Aspirin Cardio Council Advisory Board. MJB reports grants and contracts from NIH, FDA, AHA, Bayer, Novo Nordisk and Amgen; consulting fees from Novo Nordisk, Kowa, Scene Health and Huma; payment from Novo Nordisk, and participation on the boards of Novo Nordisk, Bayer, Roche, Vectura, Novartis and Merck. RC and AK are employees of AccuScript Consultancy, which was paid a fee to conduct the initial literature search and analysis. ALC has received grants and contracts from Bayer, Servier, and CellNova; payments from Novo Nordisk, AstraZeneca, Novartis, Elea, Bayer, Bagó, Raffo, and PTC; expenses paid by Novo Nordisk and PTC, and has received payment from the boards of Bayer and Gador. AL has received consulting fees from Bayer. LL has stock options in Bayer AG and is an employee of Bayer AG. OS has received payment from Bayer, Eli Lilly and Lifescan. Authors' contributions: Conceptualisation: DS, MJB, ALC, AL, LL, FS, OS and ZS; data curation: RC, AK; formal analysis: RC, AK; writing – review & editing: DS, MJB, ALC, AL, LL, FS, OS and ZS., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)