Background <p>Opportunistic infections have several complications and negative impacts on the patients and the family. Despite the improvement in the provision of antiretroviral therapy, opportunistic intestinal parasitic infections are major public health concerns, especially in areas with poor sanitation and inadequate clean water access. The burden varies considerably by socio-demographic area, drug adherence, and CD4 level. This study was conducted due to the limited findings in the study area, and it aims to explore certain variables related to opportunistic infections that have not been well studied, including social support and behavioral factors such as alcohol, smoking, and khat consumption.</p> Objective <p>To determine the prevalence of opportunistic intestinal parasitic infections and identify associated factors among patients living with HIV/AIDS attending antiretroviral therapy clinics in Central Ethiopia Regional State during 2024.</p> Methods and materials <p>An institution-based multicenter analytical cross-sectional study was conducted at selected public hospitals in the Central Regional State of Ethiopia from 21 March to 21 April, 2024. Study participants were selected using systematic random sampling. Data were collected using an interviewer-administered questionnaire and data extraction checklist. Binary logistic regression analysis was performed to identify factors associated with opportunistic intestinal parasitic infections. Variables with a p-value &lt; 0.05 at a 95% confidence interval were considered statistically significant.</p> Results <p>Three hundred and ninety-three participants were enrolled in the study; mean age 34.2 ± 14.5 years and 58.3% females. The estimated prevalence of opportunistic intestinal parasitic infections was 17.3% (95% CI: 13.6, 21.1). Cryptosporidium (51.5%) and Cyclospora (25%) were the leading causes of opportunistic parasites. The following factors were significantly associated with opportunistic intestinal parasitic infections: consuming spring or well water for drinking (AOR = 2.19, 95% CI: 1.13, 4.27), high viral load (AOR = 3.29, 95% CI: 1.67, 6.49), poor ART adherence (AOR = 6.27, 95% CI: 2.24, 17.56), low recent CD4 count (AOR = 7.54, 95% CI: 2.80, 20.27), WHO clinical stage IV (AOR = 3.14, 95% CI: 1.19, 8.27), and DM comorbidity (AOR = 4.67, 95% CI: 2.00, 10.93).</p> Conclusion and recommendation <p>In this study, 17.3% of patients were infected with opportunistic intestinal parasites. Variables such as source of drinking water, viral load, ART adherence, CD4 count, WHO clinical stage, and the presence of diabetes mellitus co-morbidity were found to be significantly associated with opportunistic intestinal parasitic infections. Patients living with HIV/AIDS need to avoid drinking spring or well water, adhere to ART, and follow all the recommendations provided by the healthcare providers. Healthcare providers and institutions need to provide a strict recommendation on drinking water preferences and ART adherence. Special attention is also required for patients with high viral load, low CD4 count, advanced disease, and chronic co-morbidities like diabetes to prevent the burden of opportunistic parasites.</p> Clinical trial number <p>Not applicable.</p>