Context Empagliflozin was found to decrease mortality in patients with type 2 diabetes mellitus (T2DM) and a prior cardiovascular disease (CVD) event. Objectives To establish whether these benefits can be replicated in a real-world setting, should be expected with the use of dapagliflozin, and apply to T2DM patients at low risk of CVD. Design General practice, population-based, retrospective cohort study (January 2013 to September 2015). Setting The Health Improvement Network database. Participants A total of 22,124 T2DM patients (4444 exposed to dapagliflozin; 17,680 unexposed T2DM patients) matched for age, sex, body mass index, T2DM duration, and smoking. Main Outcome Measures The primary outcome was all-cause mortality (high and low risk for CVD) in the total study population, expressed as the adjusted incidence rate ratio (aIRR) with 95% confidence intervals (CIs). As a secondary analysis in the low-risk population, all-cause mortality and incident CVD were considered. Results Patients with T2DM exposed to dapagliflozin were significantly less likely to die of any cause (aIRR: 0.50; 95% CI: 0.33 to 0.75; P = 0.001). Similarly, in low-risk patients, death from any cause was significantly lower in the cohort exposed to dapagliflozin (aIRR: 0.44; 95% CI: 0.25 to 0.78; P = 0.002). The difference in the risk of incident CVD did not reach statistical significance between groups in low-risk patients (aIRR: 0.89; 95% CI: 0.61 to 1.31; P = 0.546). Conclusions Patients with T2DM who were exposed to dapagliflozin had a lower risk of death from any cause irrespective of baseline CVD status.