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Objective To determine rates of, and factors associated with, disengagement from care in a decentralised antiretroviral programme. Methods Adults (≥16 years) who initiated antiretroviral therapy ( ART) in the Hlabisa HIV Treatment and Care Programme August 2004-March 2011 were included. Disengagement from care was defined as no clinic visit for 180 days, after adjustment for mortality. Cumulative incidence functions for disengagement from care, stratified by year of ART initiation, were obtained; competing-risks regression was used to explore factors associated with disengagement from care. Results A total of 4,674 individuals (median age 34 years, 29% male) contributed 13 610 person-years of follow-up. After adjustment for mortality, incidence of disengagement from care was 3.4 per 100 person-years (95% confidence interval ( CI) 3.1-3.8). Estimated retention at 5 years was 61%. The risk of disengagement from care increased with each calendar year of ART initiation ( P for trend <0.001). There was a strong association between disengagement from care and higher baseline CD4+ cell count (subhazard ratio ( SHR) 1.94 ( P < 0.001) and 2.35 ( P < 0.001) for CD4+ cell count 150-200 cells/μl and >200 cells/μl respectively, compared with CD4 count <50 cells/μl). Of those disengaged from care with known outcomes, the majority (206/303, 68.0%) remained resident within the local community. Conclusions Increasing disengagement from care threatens to limit the population impact of expanded antiretroviral coverage. The influence of both individual and programmatic factors suggests that alternative service delivery strategies will be required to achieve high rates of long-term retention. [ABSTRACT FROM AUTHOR]