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There is a scarcity of high-quality randomized controlled trials (RCTs) comparing antithrombotic regimens for secondary prevention of arterial thrombosis (AT) in antiphospholipid syndrome (APS). We reviewed different antithrombotic regimens used for this purpose. We searched for studies on management of AT in APS on PubMed and Web of Science. Eleven studies (5 RCTs, 3 prospective, and 3 retrospective cohort studies) comparing different regimens and reporting outcomes specifically for patients with index AT events were identified. Treatments were vitamin K antagonists (VKA; 9 studies), non-VKA oral anticoagulant (NOAC; 3 studies), single antiplatelet therapy (SAPT; 7 studies), dual antiplatelet therapy (DAPT; 2 studies), and VKA combined with SAPT (4 studies). We performed a meta-analysis for the outcomes: recurrent AT, any (arterial or venous) recurrent thromboembolism, and major bleeding. Recurrent AT was reduced with VKA plus SAPT versus VKA (risk ratio [RR]: 0.43; 95% confidence interval [CI]: 0.22-0.85) and with DAPT versus SAPT (RR: 0.29; 95% CI: 0.09-0.99). Any recurrent thromboembolism was reduced with VKA plus SAPT versus VKA alone (RR: 0.41; 95% CI: 0.24-0.69) and versus SAPT alone (RR: 0.36; 95% CI: 0.13-0.96). There were no significant differences between other treatments for thromboembolism and for none of the comparisons regarding major bleeding. In a sensitivity analysis, excluding low-quality studies, VKA was more effective than NOAC to prevent recurrent AT (RR: 0.25; 95% CI: 0.07-0.93). Combined antithrombotic therapy might be more effective than single agents as secondary prophylaxis in APS with AT, and does not seem to compromise with safety, but the quality of evidence is generally low. NOACs should be avoided for patients with APS and AT., Competing Interests: S.S. reports research grants from Octapharma and Boehringer-Ingelheim and honoraria from Alnylam, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, and Sanofi., (Thieme. All rights reserved.)