Introduction: Since the introduction of anti-retroviral therapy (ART) for managing human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in Nigeria, adherence to treatment has been a critical issue due to its importance in improving the quality of life of people living with HIV/AIDS (PLWHA). The aim of this paper is to determine level of adherence to ART, examine reasons for non-adherence and the association between socio-demographic characteristics, and adherence to ART among PLWHA who were attending the State Hospital, Osogbo, Nigeria. These are with the view to establishing factors influencing adherence to ART among PLWHA in Nigeria. Material and methods: The health belief model and political economy perspectives framed the paper. Purposive/systematic sampling techniques were used to select 200 PLWHA (men and women) attending clinic in the State Hospital, Osogbo, South Western Nigeria. Results: Findings indicated adherence level of 69%. Furthermore, the reasons for non-adherence were forgetfulness (21.5%), work/travel (16.0%), fasting and spiritual interruption (8.5%), inadequate meal (7.0%), stigma (7.0%), and side effect of the drug (7.0%). It was revealed that the size of the ART was too big for some of the respondents, which militated against adherence. Moreover, the socio-demographic characteristics that influenced adherence were sex, age, marital status, marriage type, education, number of children, and occupation. However, most of these influences were not statistically significant. Finally, respondents' suggestions on how to improve adherence were PLWHA should be encouraged to take their drugs (33.5%), improve the size because it is too big (10.0%), educate PLWHA (24.0%), make ART more private (9.0%), and legislation on stigma (9.5%). Conclusions: The paper concluded that health behavior of PLWHA, socio-economic, and demographic factors influenced PLWHAs adherence to ART in the study area.