Both Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) remain major public health problems in Ethiopia. Good adherence to antiretroviral therapy is necessary to achieve the best virological response, lower the risk of treatment failure and drug resistance, and reduce morbidity and mortality. There are many alterable factors known to affect the treatment adherence. In this regard, there have been very limited researches particularly in Adama. Therefore, this study was aimed to determine the adherence level and its associated factors among adult people living with HIV and attending their clinical care in Adama Hospital Medical College. A hospital based cross sectional study was conducted from October 1, 2016 -January 30, 2017 G. C in Adama Hospital Medical College among 190 PLWHA on ART. Systematic sampling method was used to select study participants. Data was collected by interviewing the clients and review of their medical records using structured questionnaire and checklist. Data entry and analysis was performed using SPSS for windows version 20.0. Descriptive statics was used to summarize socio-demographic and other variables. Bivariate and multivariate analysis was used to evaluate the association between dependent and independent variables. Level of adherence in the week before interview was 92.6. Patients whose initial ART regimen was TDF-3TC-NVP, were 8 times (COR=8.444 (1.678, 42.501)), chance of <95% adherence than patients those started ART with TDF-3TC-EFV regimen. Patients with opportunistic infection were about 8 times (COR=7. 593 (2.196, 26.248)) chance of <95% adherence than their counter group respectively. Patients whose waiting time >30 minutes were 8 times (AOR=8.019 (1.161, 55.390)) chance of <95% adherence than their counter group. The level of adherence to ART was relatively higher when compared to others studies done in Ethiopia and other developing countries. But it was sub optimal to WHO adherence level (≥ 95%). The major reasons for missing doses were forgetfulness, away from home (travel) and lack of awareness. The level of adherence was significantly associated with variables like history of opportunistic infection, longer waiting time and starting treatment with TDF-3TC-NVP. This implicates further effort are still needed to push up the adherence to the level of WHO recommendation.