OBJECTIVES: The aim of the current study is to explore and to observe the impact of cigarette smoking and alcohol use on adverse drug reactions occurrence of antiretroviral drugs among HIV/AIDS patients METHODS: Retrospective analysis of all patients diagnosed with HIV infection and on HAART therapy from Jan 2007 to Dec 2012 was conducted at infections disease department of Hospital Pulau Pinang, Malaysia. Patient socio-demographic details along with clinical features were recorded and the susceptible ADRs were observed during the study period. Data was descriptively analyzed by using statistical package for social sciences (SPSS 20).   RESULTS: Out of 743 patients that underwent HAART therapy, 314 (42.2%) patients had experienced adverse drug reactions. Out of total included patients 571 (76.8%) were male and 172 (23.1%) were female.  Among the patients, 512(68.9%) were smokers and 340 (45.8%) patients were alcohol users. A total number of 425 (57.2%) adverse drug reactions were recorded of which 269 (63.2%) were reported among smokers and 162 (38.1%) were reported among alcohol users. Univariate analysis indicates a statistical significant relationship between the smoker (p-value =0.009, 95% CI=1.111 – 2.079, Odd ratio= 1.520) and alcohol users (p-value=0.008, 95% CI=1.106 – 1.994, Odd ratio=1.485) with the occurrence of adverse drug reactions on HAART in HIV patients CONCLUSIONS: The study indicates the incidence of adverse drug reactions is significant in smokers and alcohol users on HAART therapy. Patient counselling on avoiding smoking and alcohol consumption can reduce ADRs in patients on HAART therapy.