Background information: today, HIV infection is a serious public health problem. However, the advent of highly active antiretroviral treatment (HAART) has dramatically improved the prognosis for HIV-positive patients, substantially reducing the rate of disease progression and death; but HAART Adherence is found to be critically important for the success of the therapy. Objectives: the objective of this study was to determine the degree of antiretroviral treatment adherence and its associated factors in all people living with HIV/AIDS on highly active antiretroviral therapy (HAART) and follow up at ART - units of Adamma and Jimma specialized hospitals in Oromiya regional state from July to August 2006. Methods: a cross sectional survey design, using both quantitative and qualitative methods, was used to conduct the study. A total of 459 people living with HIV/AIDS treated with highly active antiretroviral drugs invited to complete sets of variables using an interview and self-administered methods to elicit information on variables of demographic characteristics, ARV drugs, psychological & socio-environmental factors, and substance abuse, emotional distress, perceived social support, ART services & care providers respectively. Of the total respondents, 265 [57.7%] and 194 [42.3%] were females and males respectively who participated in this study. A total of 300 [65.4%] respondents were in the age range of 26-35 years while, 94 [20.5%] were in the range of 18-25 years. Adherence to antiretroviral therapy in the previous three days of the interview was measured by self-report. Initially, the percent of adherence was calculated for each drug by dividing the number of pills taken by the number of pills prescribed. Then, the percent of adherence to the antiretroviral regimen was estimated by the average of adherence to the drugs. Patients who reported an intake of 95% of the prescribed medication were considered to be adherent. Data was checked for multi-co-linearity and comparison of PLWHA who were adherent and non – adherent (taken < 95% of their doses of antiretroviral medications) groups was determined on important variables. The significance level was measured using 95% CIs of adjusted and crude odds ratios for which, P 0.05 were considered significant. Further, the independent predictors of adherence were also assessed using a sequence of two multivariate logistic regression models; so that the variables that had significant effect on adherence (p<0.05), either in the crude or adjusted model were selected for inclusion in subsequent models. ix Major findings: the overall prevalence of HAART adherence was found to be, 381[83.0%] in this study. Independent positive predictors of HAART adherence reported in this study include:- the participants who had: A perception about personal susceptibility to nonadherence threats [OR = 17.388, CI = 4.026, 75.096, p = 0.000], ability to adhere in future [OR = 7.212, CI = 3.465, 15.012, p = 0.000.], and an access to reliable pharmacy any time [OR = 7.908, CI = 3.296, 18.971, p = 0.000]; had no history of active substance use [OR =0.387, CI = 0.195, 0.768, p = 0.007], positive beliefs on the efficacy of HAART[ OR = 0.449, CI = 0.243, 0.829, p = 0.011], no ARVs side effects [OR = 0.455, CI = 0.224, 0.922, p = 0.029], had no depressed feelings in the last one month [OR = 2.16, CI = 1.32, 6.58, P = 0.001], were not using other drugs along with ARVs [OR = 2.478, CI = 1.121, 5.475, p = 0.025] and had no child under their responsibility [OR = 0.437, CI = 0.218, 0.874, p = 0.019] in the final adjusted multivariate model. Conclusions & Recommendations: therefore, based on these facts, it is helpful to recommend the following efforts to maximize patient adherence:- regimen rehearsal and other assistances must begin before patients have their first prescription filled; selecting a simple and tolerable antiretroviral regimen that matches the patient's lifestyle; and supportive environment in which family, friends, the community and care providers come together to ensure that barriers to adherence are minimized were found that the most important step toward optimizing adherence. Addis Ababa