This study examined whether longitudinal adherence profiles mediated the relationship between a brief adherence intervention and glycemic control among patients with type 2 diabetes. Adherence was assessed using the Medication Event Monitoring System. Longitudinal analysis via growth curve mixture modeling was carried out to classify patients according to patterns of adherence to oral hypoglycemic agents. Hemoglobin A1c assays were used to measure glycemic control as the clinical outcome. Across the whole sample, longitudinal adherence profiles mediated 35.2% (13.2, 81.0%) of the effect of a brief adherence intervention on glycemic control [from odds ratio (OR) = 8.48, 95% confidence interval (CI) (3.24, 22.2) to 4.00, 95% CI (1.34, 11.93)]. Our results suggest that patients in the intervention had better glycemic control largely due to their greater likelihood of adherence to oral hypoglycemic agents.