OBJECTIVES The objective was to examine the association between nonadherence to oral hypoglycemic agents and subsequent all-cause hospitalization, emergency room (ER) visit, and mortality among Medicare Part D enrollees with diabetes. METHODS This is a longitudinal retrospective cohort study. The study sample consisted of Medicare Part D enrollees with diabetes from six states (Alabama, California, Florida, Mississippi, New York, and Ohio) who had filled at least one prescription for oral hypoglycemic agents during the first 6 months of 2006. Adherence was measured using proportion of days covered (PDC). Subjects were classified as adherent (PDC ≥0.8), poor adherent (0.5≤ PDC <0.8), and very poor adherent (0RESULTS Data were available for 1,101,533 patients. Among them, 58.4% were females and the mean age was 71.7 years. About 64.9% were adherent, 11.2% were poor-adherent, and 24.0% were very poor-adherent with oral hypoglycemics. After controlling for age, gender, race, and comorbidities (Charlson comorbidity index), in comparison to adherent patients, the odds for all-cause hospital admission, ER visit, and mortality were 17.9% (OR: 1.179; 95%CI: 1.156-1.204), 6.3% (OR: 1.063; 95%CI: 1.048-1.077), and 7.1% (OR: 1.071; 95%CI: 1.037-1.106) higher for poor-adherent patients. Compared to adherent patients, those with very poor adherence were 22.9% (OR: 1.229; 95%CI: 1.211-1.247), 17.1% (OR: 1.171; 95%CI: 1.160-1.183), and 10.4% (OR: 1.104; 95%CI: 1.079-1.129) more likely to be hospitalized, have visited ER, or die during outcome measurement period. CONCLUSIONS The results suggest that nonadherence to oral hypoglycemic agents is relatively common and appears to be associated with adverse clinical outcomes. Medicare prescription drug plans should consider developing targeted interventions to improve adherence to oral hypoglycemic agents.