BACKGROUND: Disruptions in primary care practices, like ownership change, clinician turnover, and electronic health record system implementation, can stall quality improvement (QI) efforts. However, little is known about the relationship between these disruptions and practice participation in facilitated QI. METHODS: We explore this relationship using data collected from EvidenceNOW in a mixed-methods convergent design. EvidenceNOW was a large-scale facilitation-based QI initiative in small and medium primary care practices. Data included practice surveys, facilitator time logs, site visit field notes, and interviews with facilitators and practices. Using multivariate regression, we examined associations between disruptions during interventions and practice participation in facilitation, measured by in-person facilitator hours in 987 practices. We analyzed qualitative data on 40 practices that described disruptions. Qualitative and quantitative teams iterated analyses based on each other's emergent findings. RESULTS: Many practices (51%) reported experiencing 1 or more disruptions during the 3- to 15-month interventions. Loss of clinicians (31.6%) was most prevalent. In adjusted analyses, disruptions were not significantly associated with participation in facilitation. Qualitative data revealed that practices that continued active participation were motivated, had some QI infrastructure, and found value in working with their facilitators. Facilitators enabled practice participation by doing EHR-related work for practices, adapting work for available staff, and helping address needs beyond the explicit aims of EvidenceNOW. CONCLUSIONS: Disruptions are prevalent in primary care, but practices can continue participating in QI interventions, particularly when supported by a facilitator. Facilitators may benefit from additional training in approaches for helping practices attenuate the effects of disruptions and adapting strategies to help interventions work to continue building QI capacity.