HIV-associated pneumocystis pneumonia (PCP) is increasingly recognized as an important cause of severe respiratory illness in sub-Saharan Africa. Outcomes of HIV-infected patients with PCP, especially those requiring intensive care unit (ICU) admission, have not been adequately studied in sub-Saharan Africa. The aim of this study was to describe the clinical phenotype and outcomes of HIV-associated PCP in a group of hospitalized South African patients, and to identify predictors of mortality. We conducted a retrospective record review at an academic referral center in Cape Town. HIV-infected patients over the age of 18 years with definite (any positive laboratory test) or probable PCP (defined according to the WHO/CDC clinical case definition) were included. The primary outcome measure was 90-day mortality. Logistic regression and Cox proportional hazards models were constructed to identify factors associated with mortality. We screened 562 test requests between 1 May 2004 and 31 April 2015; 124 PCP cases (68 confirmed and 56 probable) were included in the analysis. Median age was 34 years (interquartile range, IQR, 29 to 41), 89 (72%) were female, and median CD4 cell count was 26 cells/mm3 (IQR 12 to 70). Patients admitted to the ICU (n = 42) had more severe impairment of gas exchange (median ratio of arterial to inspired oxygen (PaO2:FiO2) 158 mmHg vs. 243 mmHg, p < 0.0001), and increased markers of systemic inflammation compared to those admitted to the ward (n = 82). Twenty-nine (23.6%) patients were newly-diagnosed with tuberculosis during their admission. Twenty-six (61.9%) patients admitted to ICU and 21 (25.9%) admitted to the ward had died at 90-days post-admission. Significant predictors of 90-day mortality included PaO2:FiO2 ratio (aOR 3.7; 95% CI, 1.1 to 12.9 for every 50 mgHg decrease), serum LDH (aOR 2.1; 95% CI, 1.1 to 4.1 for every 500 U/L increase), and concomitant antituberculosis therapy (aOR 82; 95% CI, 1.9 to 3525.4; P = 0.021). PaO2:FiO2 < 100 mmHg was significantly associated with inpatient death (aHR 3.8; 95% CI, 1.6 to 8.9; P = 0.003). HIV-associated PCP was associated with a severe clinical phenotype and high rates of tuberculosis co-infection. Mortality was high, particularly in patients admitted to the ICU, but was comparable to other settings. Prognostic indictors could be used to inform ICU admission policy for patients with this condition.