Introduction: South Africa's government-led Central Chronic Medication Dispensing and Distribution (CCMDD) program offers people living with HIV the option to collect antiretroviral therapy at their choice of community-or clinic-based pickup points intended to increase convenience and decongest clinics. To understand CCMDD pick-up point use among people living with HIV, we evaluated factors associated with uptake of a community-versus clinic-based pick-up point at CCMDD enrolment. Methods: We collected baseline data from October 2018 to March 2020 on adults (≥18 years) who met CCMDD clinical eligibility criteria (non-pregnant, on antiretroviral therapy for ≥1 year and virologically suppressed) as part of an observational cohort in seven public clinics in KwaZulu-Natal. We identified factors associated with community-based pick-up point uptake and fit a multivariable logistic regression model, including age, gender, employment status, self-perceived barriers to care, selfefficacy, HIV-related discrimination, and perceived benefits and challenges of CCMDD. Results and Discussion: Among 1521 participants, 67% were females, with median age 36 years . Uptake of a community-based pick-up point was associated with younger age (aOR 1.18 per 10-year decrease, 95% CI 1.05-1.33), being employed ≥40 hours per week (aOR 1.42, 95% CI 1.10-1.83) versus being unemployed, no self-perceived barriers to care (aOR 1.42, 95% CI 1.09-1.86) and scoring between 36 and 39 (aOR 1.44, 95% CI 1.03-2.01) or 40 (aOR 1.91, 95% CI 1.39-2.63) versus 10-35 on the self-efficacy scale, where higher scores indicate greater self-efficacy. Additional factors included more convenient pick-up point location (aOR 2.32, 95% CI 1.77-3.04) or hours (aOR 5.09, 95% CI 3.71-6.98) as perceived benefits of CCMDD, and lack of in-clinic follow-up after a missed collection date as a perceived challenge of CCMDD (aOR 4.37,. Conclusions: Uptake of community-based pick-up was associated with younger age, full-time employment, and systemic and structural factors of living with HIV (no self-perceived barriers to care and high self-efficacy), as well as perceptions of CCMDD (convenient pick-up point location and hours, lack of in-clinic follow-up). Strategies to facilitate community-based pick-up point uptake should be tailored to patients' age, employment, self-perceived barriers to care and self-efficacy to maximize the impact of CCMDD in decongesting clinics.