Background: Highly Active Antiretroviral Therapy has changed the therapeutic approach to HIV/AIDS treatment. Due to genetic variation, there may be variability in response to HAART in different populations. Inappropriate HAART impacts directly on treatment outcomes as wells as have financial implications fragile economy of a developing country. This study was a retrospective study on the adverse effect profile of different HAART combinations in patients attending an HIV clinic at Komfo Anokye Teaching Hospital in Ghana. Methods: Systematic random sampling was used to select 500 patient records covering a period of 5 years from 2010 to 2014. The variables captured and reviewed included patients’ demographic information, HAART medication, CD4 counts and adverse drug reports. Results: Among the 12 common combinations, AZT+3TC with either EFV OR NVP accounted for more than 50%. In general, a lower CD4 count was associated with a lower adverse drug effect. After adjusting for the presence of other Anti-retrovirals in a HAART, Efavirenz was associated with higher incidence of adverse drug reactions reports than Nevirapine. However patients on nevirapine reported multiple adverse drug reactions than patients on efavirenz. Zidovudine’s adverse effect on the heamatopoietic was enhanced when it was combined with Efavirenz than with nevirapine. The worst HAART in terms of adverse drug reactions was one having both stavudine and nevirapine. Tenofovir usually used as second line was rarely associated with any peculiar adverse drug event. Conclusion: Patients attending HIV clinic in Ghana responded differently to HAART combinations commonly prescribed in Ghana.