BACKGROUND Atrial fibrillation (AF) after coronary artery bypass graft (CABG) is one of the most common complications. Its pathogenesis is multifactorial, and its prevention and management remain suboptimal. Recently, previous statin therapy has been reported to prevent occurrence of postoperative AF. This study evaluates whether pretreatment with statin protects against AF following CABG. METHODS One hundred twenty-four patients undergoing elective CABG, without previous statin treatment, were enrolled. Patients were randomized to atorvastatin 20 mg/d (n=62) or control (n=62) starting 48 hours before operation. The primary end point was incidence of postoperative AF. Secondary end points were major adverse cardiac and cerebrovascular events (MACEs) and persistent AF at 1-month, and identification of predictive marker. N-terminus pro-brain natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (CRP) were measured before surgery, immediate postoperative state, and 24 hours after surgery. RESULTS Incidence of AF was significantly lower in the atorvastatin versus in the control group (13% versus 27%, P=0.04). The incidence of MACEs at 30 days was similar between the 2 groups. There was a trend of occurrence of persistent AF at 30 days in the control group, although it was not statistically significant. (P=0.09). Postoperative peak NT-proBNP levels were significantly higher in patients with AF (P=0.032). Multivariable analysis showed that atorvastatin treatment conferred a 70% reduction in risk of AF (odds ratio 0.30, 95% confidence interval 0.09 to 0.98, P=0.046), whereas high postoperative NT-proBNP levels (>1235 pg/mL) were associated with increased risk (odds ratio 3.87, 95% confidence interval 1.14 to 13.11, P=0.030). Subgroup analysis showed that atorvastatin treatment resulted in a lower risk of atrial fibrillation in patients undergoing off-pump CABG (odds ratio 0.327, 95% confidence interval 0.109 to 0.984, P=0.040).CONCLUSIONS Pretreatment with atorvastatin 20 mg/d, initiated 48 hours before surgery, significantly reduces the incidence of postoperative AF after CABG. The benefit of pretreatment with statins seems to be persistent in patients with undergoing off-pump CABG.