Background Human immunodeficiency virus/ acquired immune deficiency syndrome (HIV/AIDS) constitutes a major global public health concern. There are an estimated 237,000 people living with HIV in Myanmar with prevalence of 0.57%, the fourth highest in South East Asia region. Specialist Hospital Waibargi (SHW) is one of the 3 main hospitals in Myanmar for HIV care and support with a cohort of nearly 2000 patients. This study was performed in SHW to evaluate the pattern and hospital outcome of various opportunistic infections (OI) in HIV-infected patients which are the principal cause of morbidity and mortality. Methods We conducted a retrospective records review study involving 370 HIV-infected patients hospitalized from October 2018 to September 2019 (1-year period). Disseminated tuberculosis (TB) was defined by concurrent involvement in at least two noncontiguous organs or miliary TB in a chest radiograph. Suggested Mycobacterium avium complex (MAC) was defined by the presence of prolonged fever not responding to anti-TB treatment and presence of generalized lymphadenopathy, hepatosplenomegaly, and pancytopenia in patients with CD4 <50 cells/mm3. Invasive fungal infection was defined by the presence of diffuse infiltrates on chest radiograph and/or generalized lymphadenopathy, hepatosplenomegaly, and pancytopenia with a response to antifungal therapy. Frequencies of individual OI were expressed as percentages. Results Among 370 patients, antiretroviral therapy (ART) was initiated in 150 patients during admission, 153 patients were already on ART (first-line/second-line/third-line/ default and restart patients), 67 were about to be initiated at a follow-up visit and 9 were defaulters. The mean age was 38.2 ± 11 years, 224 male and 146 female patients were admitted (ratio 1.5:1). Mean CD4 is 111 cells/mm3 (range 4–627 cells/mm3). In total, 322 patients (87%) had CD4 <350 cells/mm3. A total of 823 OI occurred in 370 patients. One hundred and twenty-nine patients had ≥ 2 OI. Among 823 episodes, pulmonary TB accounted 32.8% (270 patients) with 13% confirmed cases including 12 multi-drug-resistant cases. Extrapulmonary TB was 22% including 48 TB meningitis cases. Disseminated TB was found in 15.3%. The rest were sepsis (19.6%), acute gastroenteritis (4%), cryptococcal meningitis/cryptococcaemia (3%), Pneumocystis jiroveci pneumonia (PCP) (3.2%), skin fungal infection (4%), invasive fungal infection (4%), esophageal candidiasis (2.3%), Cytomegalovirus retinitis (0.6%), suggested MAC (1.7%), cerebral toxoplasmosis (0.7%), progressive multifocal leukoencephalopathy (0.8%), encephalitis (0.7%), Herpes zoster infection (0.6%). Eighty-six hospitalized patients died with a mortality rate of 23.2% mostly due to disseminated TB or fungal infection, PCP, sepsis, cryptococcal meningitis, and immune reconstitution inflammatory syndrome. The mean duration of hospitalization was 14 ± 11 days. Sixteen children (age 12–22 years) with CD4 <350 cells/mm3 were included, half were infected congenitally and mortality was 50% mostly due to disseminated TB and sepsis. Conclusion Even in the test and treat era of ART, most HIV-infected patients in the study were late presenters with advanced disease. It highlights the importance of increasing testing awareness in the community and eliminating mother to child transmission. TB was the commonest OI among HIV-infected patients and early TB diagnosis, anti-TB treatment, good adherence, and latent TB prophylaxis are the major tools to improve HIV/TB-related morbidity and mortality.