Studies have shown that interprofessional education (IPE) improves learner proficiencies, but few have measured the association of IPE with patient outcomes, such as clinical quality. To estimate the association of a multisite IPE initiative with quality of care. This study used difference-in-differences analysis of US Department of Veterans Affairs (VA) electronic health record data from July 1, 2008, to June 30, 2015. Patients cared for by resident clinicians in 5 VA academic primary care clinics that participated in the Centers of Excellence in Primary Care Education (CoEPCE), an initiative designed to promote IPE among physician, nurse practitioner, pharmacist, and psychologist trainees, were compared with patients cared for by resident clinicians in 5 regionally matched non-CoEPCE clinics using data for the 3 academic years (ie, July 1 to June 30) before and 4 academic years after the CoEPCE launch. Analysis was conducted from January 18, 2018, to January 17, 2019. Among patients with diabetes, outcomes included annual hemoglobin A1c, poor hemoglobin A1c control (ie, <9% or unmeasured), and annual renal test; among patients 65 years and older, outcomes included prescription of high-risk medications; among patients with hypertension, outcomes included hypertension control (ie, blood pressure, <140/90 mm Hg); and among all patients, outcomes included timely mental health referrals, primary care mental health integrated visits, and hospitalizations for ambulatory care-sensitive conditions. A total of 44 527 patients contributed 107 686 patient-years; 49 279 (45.8%) were CoEPCE resident patient-years (mean [SD] patient age, 59.3 [15.2] years; 26 206 [53.2%] white; 8073 [16.4%] women; mean [SD] patient Elixhauser comorbidity score, 12.9 [15.1]), and 58 407 (54.2%) were non-CoEPCE resident patient-years (mean [SD] patient age, 61.8 [15.3] years; 43 912 [75.2%] white; 4915 [8.4%] women; mean [SD] patient Elixhauser comorbidity score, 13.8 [15.7]). Compared with resident clinicians who did not participate in the CoEPCE initiative, CoEPCE training was associated with improvements in the proportion of patients with diabetes with poor hemoglobin A1c control (-4.6 percentage points; 95% CI, -7.5 to -1.8 percentage points; P < .001), annual renal testing among patients with diabetes (3.2 percentage points; 95% CI, 0.6 to 5.7 percentage points; P = .02), prescription of high-risk medications among patients 65 years and older (-2.3 percentage points; 95% CI, -4.0 to -0.6 percentage points; P = .01), and timely mental health referrals (1.6 percentage points; 95% CI, 0.6 to 2.6 percentage points; P = .002). Fewer patients cared for by CoEPCE resident clinicians had a hospitalization for an ambulatory care-sensitive condition compared with patients cared for by non-CoEPCE resident clinicians in non-CoEPCE clinics (-0.4 percentage points; 95% CI, -0.9 to 0.0 percentage points; P = .01). Sensitivity analyses with alternative comparison groups yielded similar results. In this study, the CoEPCE initiative was associated with modest improvements in quality of care. Implementation of IPE was associated with improvements in patient outcomes and may potentiate delivery system reform efforts.