Background Many studies investigating antiretroviral treatment (ART) adherence found the majority of patients had suboptimal adherence for a variety of different reasons. The study aimed to compare the ART adherence level and associated factors among adult human immune deficiency virus (HIV) positive patients on both care models in selected hospitals. Methods An institution-based comparative cross-sectional study was conducted among 463 HIV positive patients on ART. The study samples were selected using systematic random sampling, and pretested semi-structured interviewer administered questionnaire was used to collect data. Binary and multivariable logistic regression analyses were used to see the association between outcome and predictors using odds ratio with a 95% confidence interval to estimate the strength of the association. Results The study had a response rate of 445 (96.1%). Of the study participants, 325 (73%) and 120 (27%) were from the routine and appointment spacing models, respectively. Patients on the appointment spacing model had higher levels of optimum adherence (87.5% vs 74.27%, respectively; p = 0.006). Patients’ satisfaction with health service delivery (OR = 0.31, 95%: CI 0.11–0.84), antiretroviral drug dosage taken per day (OR = 3, 95%: CI 1.16–8.1), disclosure of HIV status (OR = 0.30, 95%: CI 0.09–0.93), distance from patient residency to health facility (OR = 0.11, 95%: CI 0.03–0.34), the memory aids used (OR = 0.02, 95%: CI 0.01–0.05), and type of HIV/AIDS care model (OR= 0.24, 95%: CI 0.1–0.6) were factors significantly associated with ART adherence level. Conclusion ART patients on the appointment spacing model had higher optimum ART adherence levels than those on the routine schedule due to factors like satisfaction status, disclosure status, type of memory aid used, type of ART care model used, and distance from the care facility. Therefore, promoting adherence enablers and alleviating barriers of ART adherence will improve ART adherence levels.