OBJECTIVES: To investigate the association of multiple medication compliance with healthcare utilization. METHODS: We identified patients ≥40 years of age with a diagnosis of type II diabetes and comorbid cardiovascular disease (CVD) including hypertension, coronary artery disease, and heart failure from California Medicaid claim data between 2002 and 2004. Proportion of days covered ≥0.8 was used to assess medication compliance. Multivariate two-part models were used to determine healthcare utilization in 2004 across different medication compliance statuses after controlling for confounding factors. RESULTS: A total of 21,740 patients were analyzed. Only 18% of patients were compliant with both diabetes and CVD medications, 32% compliant with only diabetes medication, and 7% with only CVD medication. Adherence to both diabetes and CVD medications was significantly associated with decreased number of emergency room (ER) visits (0.052±0.011, p<0.0001), decreased hospitalization (0.025±0.004, p<0.0001), increased number of outpatient visits (10.02±0.67, p<0.001) and increased number of prescription fills (35±0.89, p<0.0001). Mean covariate adjusted ER visits (0.26±0.62) in patients who did not fill appropriate medications or were noncompliant with medications were significantly higher than those compliant with both diabetes and CVD medications (0.19±0.42, p=0.000), or those compliant with only diabetes medications (0.21±0.46, p=0.000). Mean adjusted number of hospitalizations in patients compliant with only CVD medication (0.11±0.31, p=0.01) was significantly higher than those compliant with both diabetes and CVD medications (0.08±0.22, p=0.01) or compliant with only diabetes medication (0.08±0.20, p=0.001). CONCLUSIONS: Compliance with multiple medications was significantly associated with a decrease in the number of ER visits and hospitalizations in a California Medicaid population with type II diabetes and comorbid CVD.