- Objective: The aim of the current study was to evaluate the effect of α blockers on the cardiac outcomes of hypertensive patients who underwent myocardial perfusion imaging (MPI). Methods: A retrospective analysis of the nuclear cardiology laboratory database was performed. The study group included only hypertensive patients (n = 19 495). The cohort was divided into three groups – a reference group of no α-blocker therapy (n = 17 053), α blockers for benign prostatic hypertrophy (BPH) (n = 1164), and doxazosin for hypertension (HTN) (n = 1258). We used Cox proportional regression models to examine the patient cardiac outcomes (composite of cardiovascular mortality and myocardial infarction) adjusted for the myocardial perfusion study results. The mean age was 65 ± 11.1 years, 55% were men, and the average follow-up was 79.2 ± 37.3 months. Results: In univariate analysis, the doxazosin for HTN group had the highest rate of adverse cardiac events in comparison to the BPH and reference groups (14.1 vs. 11.3% and 8.9%, respectively, P < 0.001). After stratifying for the degree of reversibility of perfusion defect, only individuals with a moderate-to-severe perfusion defect in the doxazosin for HTN group had a significant increase in adverse cardiac events [hazard ratio 1.50 95% confidence interval (1.14–1.98)]. Conclusion: Our data show that doxazosin treatment for HTN is associated with adverse cardiac outcome only among patients with moderate-to-severe ischemia on myocardial perfusion imaging. Doxazosin and other α blockers appear to be safe in the vast majority of patients with a lesser degree of ischemia.