A cohort analysis using UK Clinical Practice Research Datalink (CPRD) was performed to compare the effects of bisoprolol, other β-blockers, and drugs other than β-blockers on the long-term risk of mortality and cardiovascular events in patients with angina. Adult patients first diagnosed with angina from 2000 to 2014, with ≥365 days of registration to first angina diagnosis and initiating monotherapies of bisoprolol, other β-blockers, or drugs other than β-blockers within 6 months of angina diagnosis were included. Incidence rates for each treatment cohort were compared using adjusted hazard ratio (HR) and 95% confidence intervals (CI) obtained from Cox regression analyses. Overall, 987 patients were treated with bisoprolol, 1348 with other β-blockers and 5272 with drugs other than β-blockers. Over the total follow-up (≤14 years), the HR of bisoprolol versus other β-blockers and drugs other than β-blockers for mortality was 0.45 (95% CI: 0.34-0.61) and 0.50 (95% CI: 0.38-0.66), respectively. The HR of bisoprolol versus other β-blockers for angina was 0.58 (95% CI: 0.50-0.68) and versus drugs other than β-blockers was 0.77 (95% CI: 0.68-0.88), respectively. For myocardial infarction, the HR of bisoprolol versus drugs other than β-blockers up to 14 years was 0.34 (95% CI: 0.23-0.52) and versus other β-blockers up to 5 years was 0.45 (95% CI: 0.27-0.75). At 5 years, the HR of bisoprolol versus other β-blockers, and drugs other than β-blockers, for arrhythmia was 0.60 (95% CI: 0.35-1.0) and 0.61 (95% CI: 0.40-0.93), respectively. In conclusion, long-term significant reduction in the risk of mortality and various cardiovascular events with bisoprolol versus other β-blockers, and drugs other than β-blockers, confirm treatment guidelines recommendation that bisoprolol is particularly well suited as the first-line treatment of angina in primary care.