Case studies of 8 primary care medical homes participating in a Massachusetts-based initiative were conducted to understand the approaches they used to operationalize medical home standards and associated barriers. All sites received their National Committee on Quality Assurance recognition as medical homes, yet varied considerably in how components were implemented. Despite this variation, they faced similar challenges to implementing and sustaining medical home standards. Variations and challenges strongly emerged in 4 areas: team-based care, scheduling and online access, identifying and managing high-risk patients, and organizing follow-up care. Our study offers insight into various pathways to medical home success, and notes areas for further study.