Aim Globally, differentiated care has been adopted across human immunodeficiency virus (HIV) treatment cascades as part of the strategies of increasing and sustaining retention in care. This study examined the impact of this new service delivery approach on adherence among patients receiving antiretroviral therapy in Imo state, Nigeria. Methods This was a cross sectional study carried at one tertiary and three secondary care hospitals selected across the state using a questionnaire. The study examined patients in three differentiated care models, and the usual care group. Collated data were analysed using the statistical product and service solutions (SPSS) version 24, at p <= 0.05 and 95% confidence level. Results A total of 542 questionnaires were successfully retrieved from the respondents. The female gender was predominant in all the groups, accounting for total average of 70.8%. The percentage of respondents with optimum adherence score (>= 96.6%) for multi-months scripting, fast track, support group, and usual care groups were 70.6,69, 97.4, 59.1 respectively. Of all the groups, the support group had the highest adherence to ART. Forgetfulness, traveling, avoidance of side effects, and feeling sick topped the reasons adduced for missing drugs. Age, place of residence, occupation and engagement of voluntary activities were socio-demographics influencing adherence. Adherence had significant association with the viral load suppression (Odds ratio = 3.147, p < 0.05, 95% C.I 2.025-4.891). Conclusion The study demonstrated that the adoption of differentiated care has enhanced patients' adherence to ART which differed across the models. There is need for continual counseling and support to the patients by healthcare providers so as to further improve adherence.