Background: Diabetes mellitus (DM) patients with comorbid hypertension (HTN) are at a higher risk of developing microvascular and macrovascular DM complications. Through guideline-driven recommendations, angiotensin- converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are highly recommended for these patients. Unfortunately, medication adherence to these products, though crucial to achieving therapeutic benefit, is frequently suboptimal. Motivational interviewing (MI) is a patient-centered collaborative communication style that is used to strengthen internal motivation for change that may prove effective in enhancing adherence. Objective: To examine the effect of an MI telephone intervention conducted by pharmacy students in improving adherence to ACEIs/ARBs among Medicare Advantage Plan (MAP) patients with both DM and HTN. Methods: A prospective study was conducted among patients enrolled in a Texas MAP. Medical claims data were used to identify patients with DM and HTN, and pharmacy claims were observed to recognize those who filled either an ACEI or an ARB during June 2014. Patients with a 6-month proportion of days covered (PDC) < 0.80 in the previous 6 months were determined nonadherent, and 75[%] of those were randomly selected to serve as potential subjects for the intervention, while 25[%] were randomly selected to serve as potential subjects for the control group. The intervention was a telephone call by a pharmacy student on rotation at the health plan, and 5 monthly follow-up calls. Before implementing calls, participating students attended a 3-day MI training course, where their proficiency for MI skills was evaluated. Refill data during the 6-month postintervention were evaluated to examine the intervention effect measured on 3 outcomes: PDC; PDC = 0.80 versus < 0.80; and discontinuation versus continuation. Multivariate linear and logistic regression models were constructed to adjust for any imbalances in baseline characteristics, including age, gender, number of other medications, regimen complexity, health low-income subsidy status, prescriber specialty, comorbidities, 6-month previous hospitalization, baseline 6-month PDC, and Centers for Medicare & Medicaid Services risk score. RESULTS: A total of 11 students participated in the intervention implementation. Patients receiving calls were randomly selected from those potential subjects for the intervention arm until a target of 250 was reached; 500 controls were randomly selected from the potential subjects for the control arm. The final cohort included in multivariate models consisted of 743 patients. Patients completing the initial call and at least 2 follow-ups were less likely to discontinue (OR = 0.29; 95[%] CI = 0.15-0.54; P < 0.001) and more likely to be adherent in the linear regression model (ß = 0.0604, P<0.001) and the logistic regression model (OR = 1.53; 95[%] CI = 1.02-2.28; P = 0.009). Other factors significantly associated with better adherence included higher baseline PDC and number of medications. Depression status was significantly associated with lower adherence. Conclusions: Patients receiving 2 or more calls had significantly better adherence and less discontinuation during the 6 months following initial calls compared with those who did not receive calls. This finding indicates that an MI-based telephone intervention by pharmacy students may be a promising intervention to improve adherence. Future research should examine the sustainability of the intervention effect for longer time periods and its influence on associated clinical outcomes.