The COMmunity Pharamcists ASSist for Blood Pressure (COMPASS-BP) study aimed to assess the effectiveness of lifestyle support programs administered in community pharmacies on hypertension control. This open-label, two-armed parallel group, cluster-randomized controlled trial included 73 pharmacies (clusters) in Japan randomized to a control or intervention group. Eligible hypertensive patients (n = 125), aged 20-75 years, received the intervention (n = 64) or the control treatment (n = 61), as dictated by their pharmacy randomization. Patients in the intervention group received brochures and healthy lifestyle advice from pharmacists using motivational interviewing methods during pharmacy visits over a 12-week period, with their usual pharmacy care. Conversely, the control group just received usual care. The main outcome measure was a change in morning systolic blood pressure (SBP) from baseline to week 12. The intervention group exhibited a decrease in morning SBP that was 6.0 mmHg greater than that of the control group (95% confidence interval [CI]: −11.0 to −0.9, p = 0.021). In a mixed-effect model for repeated measures analysis, the intergroup difference in morning SBP decrease was −4.5 mmHg (95% CI: −8.5 to −0.6, p = 0.024). Our findings indicate that implementation of a lifestyle advice program in pharmacies is feasible and may lead to reduced blood pressure.