Abstract: Highly active antiretroviral therapy has substantially improved the prognosis for HIV-infected patients globally. However, HIV infection remains a major cause of morbidity and mortality in many developing countries. The main objective of this study was to investigate the causes of hospital admission in patients receiving antiretroviral therapy in Lesotho. A 4 months cross-sectional study of HIV-infected, ART-treated adults admitted to the male and female medical wards at Queen Elizabeth II Referral Hospital in Maseru, Lesotho. A 96 patients enrolled, 62.5% were male and the median CD4 count on admission was 101 cells/μL (IQR 22-224). A 69.8% of the study participants had been receiving HAART for <6 months and 97.9% of all patients were on a first line NNRTI-based regimen. Patients were admitted for the management of opportunistic infections (71.9%), non-infectious HIV-related diseases (24.0%) and adverse drugs reactions (18.8%). The most frequent principal diagnoses were tuberculosis (45.8%), AZT-induced anaemia (11.5%), pneumonia (9.4%) and immune-inflammatory reconstitution syndrome (7.3%). In-hospital mortality among the study participants was 36.5%. HIV-related opportunistic infections are an important cause of hospital admission and mortality in the era of HAART. Efforts are needed to encourage patients to present early to HIV care. In addition, patient monitoring should be improved in order to facilitate early detection and management of treatment failure.