There is little information on patients’ medication adherence experiences at community-based clinics in Ghana. This study investigated adherence to antiretroviral medication among people living with HIV (PLHIV) attending a community-based HIV clinic. PLHIV ( N = 349) completed a questionnaire battery on medication adherence, doctor–patient communication, HIV stigma, patient general self-efficacy, perceived social support, and on patient spirituality. Linear Regression was used to analyze the data. Results showed that doctor–patient communication ( β = .38, 95% CI [0.09, 0.18], P <.001) and social support from significant others ( β = .46, 95% CI [0.18, 0.67], P <.001) were positively associated with medication adherence in this sample. In contrast, HIV stigma ( β = –.16, 95% CI [–0.58, −0.09], P <.01), patient spirituality ( β = –.22, 95% CI [–0.44, −0.00], P <.05), and patient general self-efficacy ( β = –.14, 95% CI [–0.17, −0.02], P <.01) were negatively associated with medication adherence. There is a need for educational interventions targeted at enhancing doctor–patient communication and social support while reducing stigma among PLHIV in Ghana.