BackgroundUncontrolled blood pressure (BP) increases the risk of major adverse cardiovascular events. In SPRINT an intensive versus standard BP lowering strategy resulted in a lower rate of cardiovascular events and death. Whether BP reduction only or also the choice of anti‐hypertensive drugs is associated with outcomes remains to be elucidated.AimsWe aim to study the association of BP and different anti‐hypertensive drugs with several cardiovascular outcomes.MethodsTime‐updated Cox and mixed‐effects models. The primary outcome was a composite of first myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death.ResultsA total of 9361 patients were included. The anti‐hypertensive agents most frequently used were ACEi/ARBs, with an almost 20% higher prescription rate in the intensive arm (80% vs. 61%), followed by thiazide‐type diuretics (65% vs. 42%), calcium‐channel blockers (57% vs. 39%), and beta‐blockers (52% vs. 26%). Mineralocorticoid receptor antagonists were rarely used (≤7% of the observations). In multivariate analysis, the use of ACEi/ARBs, especially in combination with thiazides, were independently associated with a lower primary outcome event‐rate (HR [95%CI] 0.75 [0.61–0.92], p = .006), whereas a DBP <60 mmHg was independently associated with a higher event‐rate (HR [95%CI] 1.36 [1.07–1.71], p = .011). SBP <120 mmHg was associated with lower rate of cardiovascular and all‐cause death on intensive treatment but not on the standard arm (interaction p < .05 for both).ConclusionsIn SPRINT, an intensive therapy strategy achieving SBP <120 mmHg with a DBP ≥60 mmHg, and using ACEi/ARBs plus thiazides was associated with a lower event‐rate.