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Background: Accreditation Council on Graduate Medical Education (ACGME) duty hour restrictions have led to the widespread implementation of non-house staff services in academic medical centers, yet little is known about the quality and efficiency of patient care on such services., Objective: To evaluate the quality and efficiency of patient care on a physician assistant/hospitalist service compared with that of traditional house staff services., Design: Retrospective cohort study., Setting: Inpatient general medicine service of a 747-bed academic medical center., Patients: A total of 5194 consecutive patients admitted to the general medical service from July 2005 to June 2006, including 992 patients on the physician assistant/hospitalist service and 4202 patients on a traditional house staff service., Intervention: A geographically localized service staffed with physician assistants and supervised by hospitalists., Measurements: Length of stay (LOS), cost of care, inpatient mortality, intensive care unit (ICU) transfers, readmissions, and patient satisfaction., Results: Patients admitted to the study service were younger, had lower comorbidity scores, and were more likely to be admitted at night. After adjustment for these and other factors, and for clustering by attending physician, total cost of care was marginally lower on the study service (adjusted costs 3.9% lower; 95% confidence interval [CI] -7.5% to -0.3%), but LOS was not significantly different (adjusted LOS 5.0% higher; 95% CI, -0.4% to +10%) as compared with house staff services. No difference was seen in inpatient mortality, ICU transfers, readmissions, or patient satisfaction., Conclusions: For general medicine inpatients admitted to an academic medical center, a service staffed by hospitalists and physician assistants can provide a safe alternative to house staff services, with comparable efficiency.