A stress–coping model was tested to examine the role that negative life events, coping methods, and depression might play in moderating the associations between HIV-related factors (ARV drug regimen, HIV staging and CD4 count) and higher-risk sexual behaviours of people living with HIV/AIDS. The model depicted hypothesised relationships among several characteristics of HIV-related variables, negative life events, coping behaviours and depression. One hundred and fifty-four HIV patients who were receiving antiretroviral therapy through the PEPFAR programme in Ibadan, Nigeria, responded to a questionnaire. In a hierarchical multiple regression analysis, variables were entered into the equation in the order specified a priori by the model. The results show that: (a) patients on the combined 3-drug ARV regimen were more likely to have engaged in higher-risk sexual behaviours as compared to those on a regimen of two or one ARV drugs; (b) negative life events and (c) a coping method characterised by HIV-status denial both predicted increased higher-risk-sexual-behaviour practice among the patients. The study underscores the need for continuous evaluation of the level of higher-risk-sexual-behaviour practice and associated factors, particularly among HIV/AIDS patients receiving ARV treatment.