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Background: In the last few years, percutaneous LAA occlusion (LAAO) has become a plausible alternative in atrial fibrillation (AF) patients with contraindications to anticoagulation therapy. Nevertheless, the optimal antiplatelet strategy following percutaneous LAAO remains to be defined. Methods: Studies comparing single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) following LAAO were systematically searched and screened. The outcomes of interest were ischemic stroke, device‐related thrombus (DRT) and major bleeding. A random‐effect meta‐analysis was performed comparing outcomes in both groups. The moderator effect of baseline characteristics on outcomes was evaluated by univariate meta‐regression analyses. Results: Sixteen observational studies with 3255 patients treated with antiplatelet therapy (SAPT, n = 1033; DAPT, n = 2222) after LAAO were included. Mean age was 74.5 ± 8.3 years, mean CHA2DS2‐VASc and HAS‐BLED scores were 4.3 ± 1.5 and 3.2 ± 1.0, respectively. At a weighted mean follow‐up of 12.7 months, the occurrence of stroke (RR 1.33; 95% CI 0.64–2.77; p =.44), DRT (RR 1.52; 95% CI 0.90–2.58; p =.12), and the composite of stroke and DRT (RR 1.26; 95% CI 0.67–2.37; p =.47) did not differ significantly between SAPT and DAPT groups. The rate of major bleedings was also not different between groups (RR 1.41; 95% CI 0.64–3.12; p =.39). Conclusions: Among AF patients at high bleeding risk undergoing percutaneous LAAO, a post‐procedural minimalistic antiplatelet strategy with SAPT did not significantly differ from DAPT regimens regarding the rate of stroke, DRT and major bleeding. [ABSTRACT FROM AUTHOR]