OBJECTIVES: To measure the effectiveness of adherence interventions for oral hypoglycemics, antihypertensives, and statins on medication adherence and acute hospitalization (emergency room [ER] and inpatient) in three Medicaid managed care organizations (MCOs) in Southeastern Pennsylvania (SEPA) and Lehigh/Capital-New West Pennsylvania (LCNWPA). METHODS: One-year follow-up analysis of prescription and hospitalization member data with prescription fills for hypoglycemics, statins, and/or antihypertensives from January 1 to December 31, 2012. Thirty interventions— categorized as general interventions (GI) for all subjects and personalized interventions (PI) for higher-risk care-managed subjects—were implemented to improve 2013 adherence.  Medication adherence (proportion of days covered [PDC]; baseline inclusion criterion: 20%–67%) and acute hospitalization rates (utilization per thousand members per year) were calculated at baseline and at one-year post-intervention. RESULTS: Of 6,382 participants (1,607 LCNWPA; 4,775 SEPA), 1,044 were PI subjects (579 LCNWPA; 465 SEPA). SEPA and LCWPA member profiles were demographically similar to one another, except regarding race and ethnicity. The PDC rate improvements for all three medication classes were 13.14% for LCNWPA and 14.15% for SEPA (P<0.01 for both), accompanied by significant increases in inpatient admissions (+11.0% and +1.9%, respectively; P<0.01 for both); the SEPA cohort also experienced an increase in inpatient admissions—small in magnitude, but statistically significant (+0.3%; P<0.01). Improvements in mean PDC were significantly greater in PI than GI subjects (LCNWPA: 16.12% vs. 11.46%, P<0.01; SEPA: 20.95% vs. 13.42%, P<0.01), but increases in acute hospitalization were also significantly greater (P<0.01 for all, except ER-[LCNWPA]) due to selection bias. Subjects demonstrating improvements in 2013 PDC rates displayed comparable changes in acute hospitalization rates as their non-improving counterparts. CONCLUSIONS: Multifaceted MCO-implemented adherence interventions significantly improved medication adherence in Medicaid participants, especially in higher-risk subjects. However, these PDC improvements were not necessarily translated into measurable reductions in acute hospitalization over the one-year post-intervention timeframe.