Background: A major challenge to antiretroviral therapy is poor adherence by the patients due to the multiplicity of drugs involved. For effective outcome of therapy, a 95% adherence is advocated in patients on ARV drugs. Objectives: Study sought to evaluate the factors that affect the adherence to their prescribed medications by people living with HIV (PLWHIV) in the capital city of Port Harcourt, South-South, Nigeria. Methods: A descriptive cross sectional study using pretested questionnaire was used to collect information on adherence among HIV adult patients. Socio-demographic factors were evaluated as possible factors associated with adherence. Reasons for missing medications were also obtained and described. Results: Participants comprised of 109 (31.8%) males and 231 (67.3%) females (mean age 37.3 ± 8.9) years. Study revealed a poor level (58%) of adherence among participants. Patient factors (forgetfulness, personal travels and work schedule), were major reasons given for missing their medications. Others are economic (lack of transport, poverty) and socio-cultural (stigma, spiritual) factors. Social support in the form of treatment supporter was found to be a significant (p<0.05) positive influencing factor to adherence by patients as well as disclosure of status to spouse. Conclusion: Strategies to improve adherence should be focused on the ways to address the negative influencing factors. Improved awareness in terms of counselling, education and orientation of the patients is strongly advocated. Social support systems (family, community, treatment supporter) and societal acceptance of PLWHIV should be put in place to encourage adherence.