Background: Peroxisome proliferator-activated receptor α (PPARα) activators reduce inflammation and oxidative stress. Inflammation plays an important role in the initiation and maintenance of atrial fibrillation (AF). It has been suggested that PPARα activators may have antiarrhythmic properties, but no clinical data exist. The objective of this study was to investigate whether the PPARα activator gemfibrozil prevents or delays the development of AF in patients with coronary heart disease. Methods: We retrospectively analyzed the electrocardiograms (ECGs) performed in the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial, a multicenter, randomized, double-blinded, secondary prevention trial of gemfibrozil and matching placebo. The ECGs were performed annually or biannually and when clinically indicated. Participants who were in AF on baseline ECG were excluded from the present analysis. Relative risk for AF was calculated from Cox regression with death as a competing risk factor. Results: A total of 12,605 ECGs from 2,130 participants were interpreted (5.9 ± 2.1 ECGs per participant, range 2-20). At baseline, the gemfibrozil (n = 1,070) and placebo (n = 1,060) groups were well matched. Mean age was 64.1 ± 7.1 years. Over 4.4 ± 1.5 years of follow-up, 123 (5.8%) participants developed new AF. There was no difference in AF incidence between the gemfibrozil and placebo groups (64/1,070 vs 59/1,060, respectively; P = .33). In Cox regression, the risk of AF was similar between the 2 study groups (hazard ratio 1.04, 95% CI 0.73-1.49, P = .82). Conclusions: In this post hoc analysis of a multicenter, double-blinded, randomized controlled trial, the PPARα activator gemfibrozil did not reduce the 4-year incidence of AF among men with coronary heart disease.