BACKGROUND:The Chronic Care Initiative (CCI) was a large state-wide patient-centered medical home (PCMH) initiative in Pennsylvania in place from [2008][2009][2010][2011]. OBJECTIVE: Determine whether the CCI impacted the utilization and costs for Medicaid patients with chronic medical conditions and comorbid psychiatric or substance use disorders. DESIGN: Analysis of Medicaid claims using difference-indifference regression analyses to compare changes in utilization and costs for patients treated at CCI practices to propensity score-matched patients treated at comparison non-CCI practices. SETTING: Ninety-six CCI practices in Pennsylvania and 60 non-CCI practices during the same time period. PARTICIPANTS: A total of 11,105 comorbid Medicaid patients treated in CCI practices and an equal number of propensity-matched comparison patients treated in non-CCI practices. MEASUREMENTS: Changes in total per-patient costs from 1 year prior to 1 year following an index episode period. Secondary outcomes included utilization and costs for emergency department (ED), inpatient, and outpatient services. RESULTS: The CCI group experienced an average adjusted total cost savings of $4145.28 per patient per year (P = 0.023) for the CCI relative to the non-CCI group. This was largely driven by a $3521.15 savings (P = 0.046) in inpatient medical costs, in addition to relative savings in outpatient psychiatric ($21.54, P < 0.001) and substance abuse service costs ($16.42, P = 0.013), compared to the non-CCI group. The CCI group, related to the non-CCI group, had decreases in expected mean counts of ED visits (for those who had any) and psychiatric hospitalizations of 15.6 (95 % CI: -21, −9) and 40.7 (95 % CI: -57, -18) percentage points respectively. LIMITATIONS: We do not measure quality of care and cannot make conclusions about the overall costeffectiveness or long-term effects of the CCI. CONCLUSIONS: The CCI was associated with substantial cost savings, attributable primarily to reduced inpatient costs, among a high-risk group of Medicaid patients, who may disproportionally benefit from care management in patient-centered medical homes.