Practice facilitation is an approach for advancing quality improvement (QI), but its success depends on effective relationships and communication among participants. Our goal was to identify patterns of contrasting perspectives on implementation issues between practice leaders and their practice facilitators, and factors that may contribute to them. We conducted individual interviews with practice leaders and the practice facilitators assigned to them as part of a program focused on preventive cardiology within primary care practices. We used summative content analysis to quantify the incidence of contrasting perspectives, and bivariate and qualitative analyses to explore relationships between contrasting perspectives and contextual factors. Among the 16 dyads, contrasting perspectives commonly related to the easiest or hardest QI interventions to implement (8 of 16 dyads) and the practice's success implementing interventions (5 of 16 dyads). There was a nonsignificant, inverse correlation (r = -0.19, p = .47) between the number of in-person QI visits from the facilitator and the total number of contrasting perspectives. Turnover of staff was frequently reported in dyads with contrasting perspectives. Although the impact of contrasting perspectives warrants additional study, planners of QI initiatives using practice facilitation should consider taking steps to minimize contrasting perspectives, or the potential adverse consequences of them, by addressing turnover challenges and encouraging opportunities to share perspectives.