Background Diabetes mellitus (DM) group clinics can effectively control hypertension, but data to support glycemic control are equivocal. This study evaluated the comparative effectiveness of 2 DM group clinic interventions on glycosylated hemoglobin (HbA1c) levels in primary care. Methods Eighty-seven participants were recruited from a DM registry of a single regional Veterans Affairs medical center to participate in an open, randomized comparative effectiveness study. Two primary care–based DM group interventions of 3 months' duration were compared. Empowering Patients in Care (EPIC) was a clinician-led, patient-centered group clinic consisting of 4 sessions on setting self-management action plans (diet, exercise, home monitoring, medications, etc) and communicating about progress with action plans. The comparison intervention consisted of group education sessions with a DM educator and dietician followed by an additional visit with one's primary care provider. Hemoglobin A1clevels were compared after intervention and at the 1-year follow-up. Results Participants in the EPIC intervention had significantly greater improvements in HbA1clevels immediately following the active intervention (8.86%-8.04% vs 8.74%-8.70% of total hemoglobin; mean [SD] between-group difference 0.67% [1.3%];P = .03), and these differences persisted at the 1 year follow-up (0.59% [1.4%],P = .05). A repeated-measures analysis using all study time points found a significant time-by-treatment interaction effect on HbA1clevels favoring the EPIC intervention (F2,85 = 3.55;P = .03). The effect of the time-by-treatment interaction seems to be partially mediated by DM self-efficacy (F1,85 = 10.39;P = .002). Conclusion Primary care–based DM group clinics that include structured goal-setting approaches to self-management can significantly improve HbA1clevels after intervention and maintain improvements for 1 year. Trial Registration clinicaltrials.gov Identifier:NCT00481286