Background/Aims: Clinical practice systems are an important component of a high functioning Patient-Centered Medical Home (PCMH). Here, the relationships between PCMH clinical practice systems and healthcare costs and utilization are examined using a retrospectively constructed longitudinal cohort receiving consistent primary care from the same medical group over a 5-year period. Methods: A 2005 survey of medical group directors measured clinical practice systems using the Physician Practice Connections®-Research Survey™ (PPC®-RS). Medical group PPC®-RS scores were compared to the annual medical costs and utilization of a cohort of 58,391 persons attributed across 22 medical groups over a 5-year period (2005-2009). Four outcomes adjusted to 2005 dollars were considered: total annualized cost, total annualized outpatient cost, total annualized inpatient cost, and annualized emergency department visits (ED). Multivariate, multilevel regressions adjusting for patient demographics, health status and autoregressive errors estimated the relationship between PPC®-RS and study outcomes. Cohort-wide associations with PPC®-RS scores as well as specific effects within three sub-cohorts (medication count: 0-2[N=29,657], 2-6[N=19,505], 7+[ N=9,229]) were considered. Results: The only consistent, cohort-wide relationship was with ED use. A 10% (71.13 to 78.24) increase in PPC®-RS scores was associated with 3.9 (medication count: 0-2), 6 (medication count: 3-6), and 11.6 (medication count: 7+) fewer ED visits/1000 in 2005; and 5.1, 7.6, and 13.6 fewer visits/1000 in 2009. The same 10% increase in PPC®-RS scores had little impact upon the least complex (medication count: 0-2) with no significant change in total ( -$22/person in 2005; $184/person in 2009), outpatient( -$11/person in 2005; $42/person in 2009), and inpatient ($26/person in 2005; $29/person in 2009) costs. For medically complex patients (medication count: 7+), the story was different. The 10% increase in PPS-RS scores was associated with significantly decreased total ($446/person in 2005; $184/person in 2009) and outpatient ($241/person in 2005; $54/person in 2009) costs, but no significant change in inpatient costs ($43/person in 2005; $46/person in 2009). Conclusions: Improved PCMH clinical practice systems appear associated with a sustained reduced reliance upon emergency care, and their association with costs appears limited to the most medically complex who would most benefit from improved management of complex disease.