OBJECTIVES: To describe the prevalence and outcome of patients admitted to a pediatric intensive care unit with viral respiratory tract infections. DESIGN: Retrospective descriptive study. SETTING: Pediatric intensive care unit in a tertiary pediatric hospital situated in Cape Town, South Africa. PATIENTS: All children (n = 195; 20% pediatric intensive care unit admissions) with positive respiratory viral isolates between April 1 and December 31, 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, laboratory, and outcome data were recorded from medical folders. Complete data were available for 175 patients (median age [interquartile range] 4.7 months [2.3-12.9 months]; 49% male). One hundred four (59.4%) patients had comorbid conditions; 30 (17%) were HIV-infected. Rhinovirus (n = 76 [39%]), respiratory syncytial virus (n = 54 [27.7%]), adenovirus (n = 30 [15.4%]), influenza A (n = 26 [13.3%]), parainfluenza (n = 23 [11.8%]), and human metapneumovirus (n = 12 [6.2%]) were most commonly isolated. Ninety-five infections (51.4%) were isolated >48 hrs after admission. Seasonal patterns were identified for respiratory syncytial virus, human metapneumovirus, and influenza A, whereas others occurred throughout the year. Twenty-five patients (14.3%) had more than one viral isolate. Presumed bacterial coinfection, which occurred in 68 (39%) patients (18 [26.5%] HIV-infected), was associated with significantly longer pediatric intensive care unit and hospital stays but not with mortality. Twenty patients died (11%, standardized mortality ratio 0.64). High Pediatric Index of Mortality scores, HIV exposure and infection, nosocomial infection, and influenza A infection were associated with mortality. CONCLUSIONS: Viral respiratory tract infection is common in this pediatric intensive care unit associated with significant morbidity and mortality, which may relate to the high burden of comorbidity and HIV.