Abstract Background Previous meta-analyses suggest that pre-procedural use of statin therapy may reduce atrial fibrillation (AF) following invasive cardiac interventions (coronary artery by-pass grafting and percutaneous coronary intervention). However, the current evidence on the benefit of statins unrelated to invasive cardiac interventions has not been clarified systematically. Methods Through a systematic literature search, trials examining the effect of statin therapy on AF were selected. Trials using statins before any percutaneous or surgical cardiac interventions were excluded. Results The search identified 11 randomized and 16 observational eligible studies, totaling 106,640 patients receiving statin therapy and 129,305 serving as controls. Fourteen studies investigated the effect of statins on new-onset AF, 13 studies investigated the effect of statins on recurrent AF and one in both new-onset and recurrent AF. In the statin versus control group the mean age was 60.7±8.3 versus 68.6±6.2years and females comprised 8.4% versus 10.3%. Statin therapy was associated with significant reduction of AF (Risk ratio (RR): 0.81 [95% confidence interval (CI): 0.80–0.83], p<0.001) combining all studies. Assessing exclusively randomized trials, statin therapy showed no significant risk reduction (RR: 0.97 [95%CI: 0.90–1.05], p=0.509), heterogeneity p>0.05. Assessing exclusively observational studies the risk reduction of new-onset AF was 12% (RR: 0.88 [95%CI: 0.85-0.91], p<0.001) and recurrent AF 15% (RR: 0.85 [95%CI: 0.80–0.90], p<0.001), heterogeneity p<0.001. Conclusion The hitherto published randomized clinical trials do not support a beneficial effect of statins on AF in patients not undergoing invasive cardiac interventions. This is in contrast to the results of observational and interventional studies.