Background Prolonged hospitalization places a significant burden on healthcare resources. Compared to the general population, hospital length of stay (LOS) is generally longer in HIV-positive patients. We identified predictors of prolonged hospital length of stay (LOS) in HIV-positive patients presenting to an emergency department (ED). Methods In this cross-sectional study, HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult ED were prospectively enrolled between 07 July 2017 and 18 October 2018. Data was subjected to univariate and multivariate logistic regression to determine parameters associated with a higher likelihood of prolonged hospital LOS, defined as [greater than or equal to]7 days. Results Among the 1224 participants that were enrolled, the median (IQR) LOS was 4.6 (2.6-8.2) days, while the mean (SD) LOS was 6.9 (8.2) days. On multivariate analysis of the data, hemoglobin Conclusion Various clinical and laboratory parameters are useful in predicting prolonged hospitalization among HIV-positive patients presenting to the ED. These parameters may be useful in guiding clinical decision making and directing the allocation of resources.