BACKGROUND: The 2001 Institute of Medicine (IOM) report highlighted the need for transformation of the U.S. health care system. This rigorous qualitative evaluation of transformational change for patient access in one large multispecialty group practice identifies the major issues facing organizations addressing the IOM challenge. METHODS: Semistructured depth interviews were conducted with the medical and administrative leaders at all levels, physicians, and nurses from 17 primary care clinics in one integrated medical group two years after they began to transform their approach to primary care patient appointment access. RESULTS: The mean time to third-next-available appointment was reduced by 76% during one year, from 17.8 days to 4.2 days. Nine important issues related to the change process were identified from clinic interviews. When combined with issues identified by central leaders, 13 themes stood out as lessons in transformational change. A major issue is the tension between physician autonomy and both effective organizational function and putting patients first. Physician autonomy is also diminished by the need to standardize and systematize care. CONCLUSIONS: Transformational change in care delivery is possible in large and complex group practices. Changes that directly affect care delivery and physician autonomy present particular challenges to physicians that need to be attended to if the changes are to be successful.