Group prenatal care improves perinatal outcomes, but implementing this complex model places substantial demands on settings designed for individual care. To describe perceived barriers and facilitators to implementing and sustaining CenteringPregnancy Plus (CP+) group prenatal care, 24 in-depth interviews were conducted with 22 clinicians, staff, administrators, and study personnel in six of the 14 sites of a randomized trial of the model. All sites served low-income, minority women. Sites for the present evaluation were selected for variation in location, study arm, and initial implementation response. Implementing CP+ was challenging in all sites, requiring substantial adaptations of clinical systems. All sites had barriers to meeting the model's demands, but how sites responded to these barriers affected whether implementation thrived or struggled. Thriving sites had organizational cultures that supported innovation, champions who advocated for CP+, and staff who viewed logistical demands as manageable hurdles. Struggling sites had bureaucratic organizational structures and lacked buy-in and financial resources, and staff were overwhelmed by the model's challenges. Findings suggested that implementing and sustaining health care innovation requires new practices and different ways of thinking, and health systems may not fully recognize the magnitude of change required. Consequently, evidence-based practices are modified or discontinued, and outcomes may differ from those in the original controlled studies. Before implementing new models of care, clinical settings should anticipate model demands and assess capacity for adapting to the disruptions of innovation. © 2015 Wiley Periodicals, Inc.