Background: South Africas government has significantly improved access to antiretroviral treatment. However, antiretroviral treatment adherence remains a significant challenge in Helen Joseph Hospital. A rate of adherence of 95% to 100% is necessary to achieve the intended outcomes of antiretroviral treatment. ARV adherence is affected by numerous factors, but long waiting times are a major concern at Themba Lethu clinic. Objective: This study aimed to examine the factors associated with ARV therapy non-adherence amongst HIV-Patients at Helen Joseph Hospital. Methods: The study used a case-control design. EPINFO 7.2 was used to calculate crude odds ratios, and SPSS Version 26 was used to conduct multivariate logistic regression to compute adjusted odds ratios, 95% confidence intervals, and P-values. In total, 322 questionnaires were administered to each participant during their clinic visit. Results: In total, there were 322 (100%) study participants, of which 51% (n=165) were non-adherent to ARV therapy. Treatment non-adherence was associated with long waiting times in Helen Joseph, Themba Lethu clinic, after adjusting for gender, age, educational level, and employment status. The adjusted odds ratio was 4.78, 95% confidence interval: (1.12 -20.42), and p value=0.04. Conclusions: The study explored factors associated with ARV treatment defaulting in Helen Joseph hospital. Long waiting times were strongly correlated with ARV treatment non-adherence in Helen Joseph hospital. If clinic waiting times are reduced, ARV treatment adherence can be improved.   Contribution: To achieve an adherence rate of 95% to 100%, the Helen Joseph Hospital has to reduce patient waiting times. Managers need to formulate strategies and redesign health systems to reduce waiting times.