Introduction: Atrial fibrillation (AF) is a common arrhythmia that can impair quality of life and increase cardiovascular mortality. Previous studies have shown potentially better outcomes with rate-control agents in patients with coronary artery disease (CAD). Yet, optimal treatment of AF is not yet known. Methods: Leveraging data from the AFFIRM trial, we performed a post-hoc analysis examining outcome differences in patients on rate vs. rhythm-control agents, based on CAD status. The primary outcome was defined as death from any cause; secondary outcomes included ischemic stroke, major bleeding, and hospitalization after baseline. Univariate and multivariate modeling were used to determine risk factors associated with designated outcomes. Results: Of 4060 patients enrolled, 1551 patients had CAD at baseline. There were no differences in treatment randomization based on CAD status; however, more patients with CAD had worse heart function and comorbid CHF. More patients with CAD ultimately used some form of rate-control compared to those without. Overall, CAD patients were more likely to experience death (HR 2.08 [1.79-2.42], P<0.001), specifically those on rhythm-control (HR 1.24 [1.01-1.52], P=0.04, Figure). CAD patients were also more likely to have ischemic stroke (HR 1.24 [1.00-1.53], P=0.05). When comparing CVD vs. non-CVD death, only CAD patients on rhythm-control exhibited a significantly higher rate of CVD death (HR 1.39 [1.03-1.89], P=0.03), while no differences in primary outcomes were noted for all other groups (P>0.05, Figure). In multivariate modeling, the effect of treatment arm on risk of CVD death in CAD patients diminished upon accounting for age, smoking, rhythm at randomization, first episode of AF, CHF, and LVEF<50% (HR 1.18 [0.93-1.50], P=0.17). Conclusions: AF patients with CAD on rhythm-control agents exhibited worse CVD outcomes, which may be more reflective of heart disease severity rather than treatment effects.