Background: Few studies have evaluated the effect of chronic calcium-channel blocker therapy (CCB) on the angiographic and clinical outcome of radial artery (RA) grafts used for coronary bypass surgery. Objectives: The purpose of this study was to evaluate if CCB influences midterm clinical and angiographic outcomes of RA grafts. Methods: Patient-level data of 6 angiographic randomized trials evaluating RA graft status at midterm follow-up were joined in this observational analysis. Cox regression and propensity score methods were used to evaluate the effect of CCB on the incidence of a composite of major adverse cardiac events (MACE) (death, myocardial infarction, and repeat revascularization) and graft occlusion. Results: The study population included 732 patients (502 on CCB). The median clinical follow-up was 60 months. The cumulative incidence of MACE at 36, 72, and 108 months was 3.7% vs. 9.3%, 13.4% vs. 17.6%, and 16.8% vs. 20.5% in the CCB and no CCB groups, respectively (log-rank p = 0.003). Protocol-driven angiographic follow-up was available in 243 patients in the CCB group and 200 in the no CCB group. The median angiographic follow-up was 55 months. The cumulative incidence of RA occlusion at 36, 72, and 108 months was 0.9% vs. 8.6%, 9.6% vs. 21.4%, and 14.3% vs. 38.9% in the CCB and no CCB groups, respectively (log-rank p < 0.001). After controlling for known confounding, CCB therapy was found to be consistently associated with a significantly lower risk of MACE (multivariate Cox hazard ratio: 0.52; 95% confidence interval: 0.31 to 0.89; p = 0.02) and RA graft occlusion (multivariate Cox hazard ratio: 0.20; 95% confidence interval: 0.08 to 0.49; p < 0.001). Conclusions: In patients with RA grafts CCB is associated with significantly better midterm clinical and angiographic RA outcomes.