Background In a large statewide initiative, New York State implemented collaborative care (CC) from 2012 to 2014 in 32 primary care settings where residents were trained and supported its sustainability through payment reforms implemented in 2015. Twenty-six clinics entered the sustainability phase and six opted out, providing an opportunity to examine factors predicting continued CC participation and fidelity. Methods We used descriptive statistics to assess implementation metrics in sustaining vs. opt-out clinics and trends in implementation fidelity 1 and 2 years into the sustainability phase among sustaining clinics. To characterize barriers and facilitators, we conducted 31 semi-structured interviews with psychiatrists, clinic administrators, primary care physicians, and depression care managers (24 at sustaining, 7 at opt-out clinics). Results At the end of the implementation phase, clinics opting to continue the program had significantly higher care manager full-time equivalents (FTEs) and achieved greater clinical improvement rates (46% vs. 7.5%, p = 0.004) than opt-out clinics. At 1 and 2 years into sustainability, the 26 sustaining clinics had steady rates of depression screening, staffing FTEs and treatment titration rates, significantly higher contacts/patient and improvement rates and fewer enrolled patients/FTE. During the sustainability phase, opt-out sites reported lower patient caseloads/FTE, psychiatry and care manager FTEs, and physician/psychiatrist CC involvement compared to sustaining clinics. Key barriers to sustainability noted by respondents included time/resources/personnel (71% of respondents from sustaining clinics vs. 86% from opt-out), patient engagement (67% vs. 43%), and staff/provider engagement (50% vs. 43%). Fewer respondents mentioned early implementation barriers such as leadership support, training, finance, and screening/referral logistics. Facilitators included engaging patients (e.g., warm handoffs) (79% vs. 86%) and staff/providers (71% vs. 100%), and hiring personnel (75% vs. 57%), particularly paraprofessionals for administrative tasks (67% vs. 0%). Conclusions Clinics that saw early clinical improvement and who invested in staffing FTEs were more likely to elect to enter the sustainability phase. Structural rules (e.g., payment reform) both encouraged participation in the sustainability phase and boosted long-term outcomes. While limited to settings with academic affiliations, these results demonstrate that patient and provider engagement and care manager resources are critical factors to ensuring sustainability.