Objective To examine the relationship between medical home transformation and patient experience of chronic illness care. Study Setting Thirteen safety net clinics located in five states enrolled in the Safety Net Medical Home Initiative. Study Design Repeated cross‐sectional surveys of randomly selected adult patients were completed at baseline (n = 303) and postintervention (n = 271). Data Collection Methods Questions from the Patient Assessment of Chronic Illness Care (PACIC) (100‐point scale) were used to capture patient experience of chronic illness care. Generalized estimating equation methods were used to (i) estimate how differential improvement in patient‐centered medical home (PCMH) capability affected differences in modified PACIC scores between baseline and postintervention, and (ii) to examine cross‐sectional associations between PCMH capability and modified PACIC scores for patients at completion of the intervention. Principal Findings In adjusted analyses, high PCMH improvement (above median) was only marginally associated with a larger increase in total modified PACIC score (adjusted β = 7.7, 95 percent confidence interval CI: −1.1 to 16.5). At completion of the intervention, a 10‐point higher PCMH capability score was associated with an 8.9‐point higher total modified PACIC score (95 percent CI: 3.1–14.7) and higher scores in four of five subdomains (patient activation, delivery system design, contextual care, and follow‐up/coordination). Conclusions We report that sustained, 5‐year medical home transformation may be associated with modest improvement in patient experience of chronic illness care for vulnerable populations in safety net clinics.