A cross sectional study is designed to assess the prevalence of adverse drug reactions and its associated factors on who are already under Highly Active Antiretroviral Therapy. Considerable progress has been made to access the therapy since the decades, even though; currently five million people do not have an access to HIV therapy, it just represents 35% only. The objective of present research is to assess the prevalence of ADRs and its associated factors on HAART at Jimma University Specialized Hospital. The data was pooled by reviewing the previous clinical records of HIV positive adults, who admitted from January 2010 to December 2013. The total sample size is found to be 233. The results showed from the total of 233 patients, 70.8% were developed ADRs and the most of them are nausea, vomiting and diarrhea at 18.9%, 15% and 7.7% respectively, and the least one is hepatotoxicity at 0.43% only. The prevalence of ADRs of HAART was high at JUSH. Low CD 4 cell count was identified at initial stages and concomitant use of cotrimoxazole with ARVs is the major risk factor for ADRs. Thus, health care providers working in the JUSH ART clinic need to monitor the CD 4 count of patients, particularly those treated with combination of antibiotics and ARVs.