Background Adverse effects from antiretroviral therapy (ART) have an impact on quality of life and medication adherence. There is no clear understanding of how people manage the adverse effects of ART. The individual taking medications which cause serious adverse effects may choose to stop or reduce the medications to relieve the adverse effects. Hence, this study was aimed at assessing coping strategies for adverse effects of ART among adult human immunodeficiency virus (HIV) patients. Methods A cross-sectional study was conducted at HIV clinic of University of Gondar Referral Hospital (UoGRH). A total of 394 study participants were recruited by systematic random sampling. Data were collected through interviewing patients. Data were entered to Epi-Info 3.5.4 and analyzed using SPSS-20.0. Descriptive statistics were used to summarize patient's sociodemographic data and the adverse effects of their ART regimen. Binary and multivariate logistic regressions were used to investigate the potential predictors of nonadherence coping strategies. Results The majorities of study participants were females (66%) and aged between 35 and 44 years (38.1%). The major adverse effects reported by the participants were headache (48.2%) followed by fatigability (18%) and loss of appetite (17.5%). Coping strategies used by HIV patients for adverse effect of ART were positive emotion coping strategy (91.1%), social support seeking (76.6%), taking other medications (76.6%), information seeking (48.7%), and nonadherence (35.5%). Younger age (AOR = 29.54, 95% CI = 2.49–35.25, p = 0.007), low level of education (AOR = 5.70, 95% CI = 2.16-15.05, p < 0.001), and living far from the health institution (AOR = 2.68, 95% CI = 1.29–5.57, p = 0.008) were associated with nonadherence coping strategy to relieve the adverse effects of ART. Conclusion The present study revealed that positive emotion coping was the most commonly used strategy. Age, level of education, and distance from health institution were the predictors of nonadherence coping strategy.