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Background Hospital-acquired infection (HAI) is a significant cause of increased morbidity and mortality amongst hospitalized patients and represents a considerable health and economic burden worldwide. However, evidence about HAI in pediatric ICU is limited. Objective To identify the prevalence of hospital-acquired infection (HAI), clinical profile, and its risk factors for nosocomial infection in patients admitted to the pediatric intensive care unit (PICU). Methodology From a two-year retrospective chart review admitted from 2019 to 2020 to the PICU, 223 patients were selected by systematic random sampling. Data were analyzed in SPSS version 23.0. P-values <0.05 were considered significant for all tests. Results Forty-five (20.2%) patients developed nosocomial infection (NI). The median age was 4 years with 25–50th IQR of (0.6–9). About invasive procedures done, the most common was nasogastric tube (57%), followed by mechanical ventilation (17.9%) and urinary catheter (13.9%). The main focus of the infection was chest (53.3%), followed by bloodstream infection (22%) and gastrointestinal infection (9%). The odds of HAI were 3.3 times higher among under-five compared to those aged between 5 and 18 years (AOR: 3.3, 95% CI = 1.4–8.0, p = 0.008). The odds of HAI were also 4.1 times higher in those who stayed for more than two weeks compared to those who stayed in the pediatric ICU 2 to 14 days (AOR: 4.1, 95% CI = 2.0–8.6, p < 0.001). The mean duration of mechanical ventilation in those patients with and without NI was 1.65 days and 13.96 days, respectively (AOR = 3.46, 95% CI = 1.44–9.81, p = 0.02). Patients who started antibiotics at admission and patients who were on nasogastric tube feeding were also statistically significant risk factors for developing NI (AOR = 2.67, 95% CI = 1.37–9.64, p = 0.02; AOR = 2.45, 95% CI = 1.64–6.53, p = 0.03). Conclusion The rate of infection in this study was higher compared to some developing countries. Younger age and prolonged length of hospital stay were found to be significant risk factors for HAI.