Background: The community client-led ART delivery groups (CCLADs) was introduced as one of the strategies to better serve individual needs and reduce unnecessary burdens on the health system. However, no study has comprehensively explained what are the drivers and barriers of CCLADs in improving treatment outcomes. This study sought to assess the barriers and facilitators of ART adherence among HIV positive patients attending CCLADs at Lira Regional Referral Hospital (LRRH), Lira District.Method: We employed a mixed methodology involving 150 study participants between July to August 2020. Quantitative data was obtained from all the participants that were picked through systematic random sampling using a semi-structured questionnaire. Data was entered into SPSS version 23.0 and analyzed at 95% level of significance. We conducted 25 in-depth interviews guided by a checklist. Qualitative data was analyzed through thematic content analysis of major themes that emerged from participants’ responses.Results: Our study found that majority 94.7% (142/150) of the respondents had an optimal adherence (100%) calculated retrospectively based on a 4-day pill uptake recall. In addition, 39.3% (59/150) of participants in CCLADs at LRRH had missed taking a pill in a period of at least 4 weeks. Among all the 104 respondents that had ever missed a medication, the most frequent reason (35% (35/104)) for missing a medication was travelling far away.From qualitative data, social support, patient self-motivation, health education and counselling and guidance were the major facilitators to adherence. On the other hand, lack of food, stigma, forgetfulness, stress, unfair hospital staffs and cultural beliefs were the major perceived barriers to ART adherence.Conclusion/recommendation: Good adherence was attributed to availability of ART at the clinic and an efficient delivery strategy. More health care follow up interventions should be designed to ensure total pill uptake by PLWHIV in communities.