OBJECTIVE: To examine protocol adherence to structured intensive management in the Valsartan Intensified Primary carE Reduction of Blood Pressure (VIPER-BP) study involving 119 primary care clinics and 1562 randomized participants. METHODS: Prospective criteria for assessing adherence to treatment prescription, uptitration, and visit attendance at 6, 10, 14, and 18 weeks postrandomization were applied to 1038 intervention participants. Protocol adherence scores of 1-5 (least to most adherent) were compared to blood pressure (BP) control during 26 weeks of follow-up. RESULTS: Mean age was 59.3 ± 12.0 years, 963 (62%) were men, and 1045 (67%) had longstanding hypertension. Clinic attendance dropped from 91 (week 6) to 83% (week 26) and pharmacological instructions were followed for 93% (baseline) to 61% at week 14 (uptitration failures commonly representing protocol deviations). Overall, 26-week BP levels and BP target attainment ranged from 132 ± 14/79 ± 9 and 51% to 141 ± 15/83 ± 11  mmHg and 19% in those participants subject to the highest (n = 270, 26%) versus least (n = 148, 14%) per protocol adherence, respectively; adjusted relative risk (RR) 1.22 per unit protocol adherence score, 95% confidence interval (CI) 1.15-1.31; for achieving BP target (P < 0.001). Participants with a per protocol score of 4 or 5 (512/1038, 49.3%) were 1.54-fold (95% CI 1.31-1.81; P < 0.001) more likely to achieve their individual BP target compared with usual care. Clinics equipped with a practice nurse significantly influenced protocol adherence (adjusted RR 1.20, 95% CI 1.06-1.37; P = 0.004) and individual BP control (RR 1.21, 95% CI 1.04-1.41; P = 0.015).