Multiple indices are available to measure medication adherence behaviors. Medication adherence measures, however, have rarely been extracted from electronic health records (EHRs) for population-level risk predictions. This study assessed the value of medication adherence indices in improving predictive models of cost and hospitalization. This study included a 2-year retrospective cohort of patients younger than age 65 years with linked EHR and insurance claims data. Three medication adherence measures were calculated: medication regimen complexity index (MRCI), medication possession ratio (MPR), and prescription fill rate (PFR). The authors examined the effects of adding these measures to 3 predictive models of utilization: a demographics model, a conventional model (Charlson index), and an advanced diagnosis-based model. Models were trained using EHR and claims data. The study population had an overall MRCI, MPR, and PFR of 14.6 ± 17.8, .624 ± .310, and .810 ± .270, respectively. Adding MRCI and MPR to the demographic and the morbidity models using claims data improved forecasting of next-year hospitalization substantially (eg, AUC of the demographic model increased from .605 to .656 using MRCI). Nonetheless, such boosting effects were attenuated for the advanced diagnosis-based models. Although EHR models performed inferior to claims models, adding adherence indices improved EHR model performances at a larger scale (eg, adding MRCI increased AUC by 4.4% for the Charlson model using EHR data compared to 3.8% using claims). This study shows that medication adherence measures can modestly improve EHR- and claims-derived predictive models of cost and hospitalization in non-elderly patients; however, the improvements are minimal for advanced diagnosis-based models.