Lipid-lowering therapy (LLT) decreases mortality in select patient populations. LLT has also been shown to have antiarrhythmic effects, thus favorably influencing the incidence and recurrence of atrial fibrillation (AF). However, data are lacking regarding the effect of LLT on mortality in patients with AF. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study was the one of the largest multicenter trials comprising of 4,060 patients with AF at high risk for stroke and death. This is a post hoc analysis of the National Heart, Lung, and Blood Institute limited-access dataset of AFFIRM patients who were on LLT at the time of randomization (n = 913). The control group consisted of AFFIRM patients who were not on LLT (n = 3,147). Cox proportional hazards analysis was performed controlling for baseline differences. The end point was all-cause mortality, cardiovascular mortality, and ischemic stroke. A separate analysis was carried out for the combined end point of death, ventricular tachycardia, ventricular fibrillation, cardiac arrest, ischemic stroke, major bleeding, systemic embolism, pulmonary embolism, and myocardial infarction. Patients on LLT were younger and on more cardioactive medications but also had more cardiovascular morbidities. On multivariate analysis, LLT use was associated with lower all-cause mortality (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.62 to 0.95, p = 0.01), cardiovascular mortality (HR 0.71, 95% CI 0.53 to 0.95, p = 0.02), ischemic stroke (HR 0.56, 95% CI 0.36 to 0.89, p = 0.01), and combined end point (HR 0.81, 95% CI 0.69 to 0.96, p = 0.01). In conclusion, a decrease in mortality and adverse cardiovascular events was observed using LLT in AF.