BACKGROUND:Research on the effects of patientcentered medical homes on quality and cost of care is mixed, so further study is needed to understand how and in what contexts they are effective. OBJECTIVE: We aimed to evaluate effects of a multi-payer pilot promoting patient-centered medical home implementation in 15 small and medium-sized primary care groups in Colorado. DESIGN: We conducted difference-in-difference analyses, comparing changes in utilization, costs, and quality between patients attributed to pilot and non-pilot practices. PARTICIPANTS: Approximately 98,000 patients attributed to 15 pilot and 66 comparison practices 2 years before and 3 years after the pilot launch. MAIN MEASURES: Healthcare Effectiveness Data and Information Set (HEDIS) derived measures of diabetes care, cancer screening, utilization, and costs to payers. KEY RESULTS: At the end of two years, we found a statistically significant reduction in emergency department use by 1.4 visits per 1000 member months, or approximately 7.9 % (p=0.02). At the end of three years, pilot practices sustained this difference with 1.6 fewer emergency department visits per 1000 member months, or a 9.3 % reduction from baseline (p=0.01). Emergency department costs were lower in the pilot practices after two (13.9 % reduction, p<0.001) and three years (11.8 % reduction, p=0.001). After three years, compared to control practices, primary care visits in the pilot practices decreased significantly (1.5 % reduction, p=0.02). The pilot was associated with increased cervical cancer screening after two (12.5 % increase, p<0.001) and three years (9.0 % increase, p<0.001), but lower rates of HbA1c testing in patients with diabetes (0.7 % reduction at three years, p=0.03) and colon cancer screening (21.1 % and 18.1 % at two and three years, respectively, p<0.001). For patients with two or more comorbidities, similar patterns of association were found, except that there was also