The objectives of this study were to compare indices of 24-hour blood pressure (BP) following a physician-pharmacist collaborative intervention and to describe the associated changes in antihypertensive medications. This was a secondary analysis of a prospective, cluster-randomized clinical trial conducted in 6 family medicine clinics randomized to co-managed (n=3 clinics, 176 patients) or control (n=3 clinics, 198 patients) groups. Mean ambulatory systolic BP (SBP) was significantly lower in the co-managed vs the control group: daytime BP 122.8 mm Hg vs 134.4 mm Hg (P<.001); nighttime SBP 114.8 mm Hg vs 123.7 mm Hg (P<.001); and 24-hour SBP 120.4 mm Hg vs 131.8 mm Hg (P<.001), respectively. Significantly more drug changes were made in the co-managed than in the control group (2.7 vs 1.1 changes per patient, P<.001), and there was greater diuretic use in co-managed patients (79.6% vs 62.6%, P<.001). Ambulatory BPs were significantly lower for the patients who had a diuretic added during the first month compared with those who never had a diuretic added (P<.01). Physician-pharmacist co-management significantly improved ambulatory BP compared with the control group. Antihypertensive drug therapy was intensified much more for patients in the co-managed group.