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Background The World Health Organization and Uganda Ministry of Health recommend differentiated service delivery models (DSDM) as patient-focussed approaches for delivering antiretroviral therapy for people living with HIV/AIDS (PLHIV) who have undetectable viral loads. We sought to determine the factors significantly associated with patient satisfaction with ART services amongst PLHIV enrolled in DSDMs. Methods This was a cross-sectional study of a random sample of PLHIVs accessing ART within DSDMs at nine facilities in East Central Uganda. Eligible patients were adult PLHIVs active on ART and enrolled in a DSDM (Community Client Led ART Delivery (CCLAD), Community Drug Distribution Points (CDDP) and Fast-Track Drug Refill (FTDR) models) for at-least twelve months. Data was collected over two months (June-July 2019). A validated tool was used to assess PLHIV satisfaction with service delivery in DSD. Logistic regression was used to establish factors associated with patient satisfaction with DSD services. Results Overall out of the 842 participants enrolled onto the study, 530(63.5%) accessed HIV care through CDDPs, 166(20.1%) through CCLAD, and 146 (16.3%) through FTDR DSDMs. Generally, 541 (64.2%) were satisfied with DSDM services : 78.7% in CDDP, 42.8% in CCLAD and 36.3% in CCLAD. The factors associated with patient satisfaction were being on CDDP [aOR = 3.42, 95% CI = 2.15–5.44] and FTDR[aOR = 2.92, 95% CI = 1.34–6.31] DSDMs relative to CCLAD, greater than three years on DSDM [aOR = 2.32, 95% CI = 1.12–4.87], lower transport costs (< $ 1.35) per clinic visit [aOR = 2.39, 95% CI = 1.59–3.60] being employed either in agriculture[aOR = 4.41, 95% CI = 2.62–7.41] or any other employment sector [aOR = 4.22, 95% CI = 2.46–7.27]relative to being unemployed, participation of a friend/relative [aOR = 1.79, 95% CI = 1.22–2.61] and not drinking alcohol [aOR = 2.33, 95% CI = 1.24–4.29]. Conclusions The study highlighted that 64.2% of the patients are satisfied with services in DSDM. Service delivery factors (DSDM model type, time spent in DSDM, and having friend or relative enrolled at the ART point providing social support), social factors (employment, and alcohol consumption), and transport costs were all associated with patient satisfaction with DSDM. Implementers of DSDMs need to further adapt services to address these factors to improve patient satisfaction in DSDMs.