Introduction: Postoperative atrial fibrillation (POAF) is a frequently reported complication of cardiac surgery, leading to increased in-hospital and long-term mortality rates. Many studies have suggested using statins to protect against POAF. Thus, we aim to investigate if statin pre-treatment may effectively lower the incidence of POAF. Method: We performed a systematic literature search of PubMed for potential studies between January 2006 and August 2021. Principal inclusion criteria were: randomized clinical trials study design; statin-naive patients; total study participants ≥ 50 units. We used the fixed-effects model to obtain the odds ratio (OR) and 95% confidence interval (CI) for each analyzed intervention. Results: Overall, statin pre-treatment reduced the incidence of POAF compared to placebo (OR 0.71; 95% CI: 0.60-0.85, p-value < 0.00001). Analyzing subclasses, atorvastatin was associated with lower incidence of POAF (OR 0.54; 95% CI: 0.41-0.70, p-value = 0.002), but rosuvastatin was not (OR 0.90; 95% CI: 0.71-1.14, p-value = 0.38). Selecting studies with ≥ 199 patients, results were divergent. There was not statistically significant difference between statin pre-treatment and placebo (OR 0.89; 95% CI: 0.74-1.09, p-value = 0.26), as well as for atorvastatin (OR 0.74; 95% CI: 0.54-1.03, p-value = 0.08) and rosuvastatin (OR 0.87; 95% CI: 0.68-1.12, p-value = 0,29). Conclusion: Statin pre-treatment before cardiac surgery is not associated with a significant reduction in POAF occurrence. Thus, based upon our results and considering possible renal complications, we discourage statin pre-treatment in preventing POAF.