Background Two-thirds of antibiotic prescriptions administered in pediatric inpatient care are inappropriate. This inappropriate utilization is associated with the emergence of antimicrobial resistance (AMR) and a decline in antibiotic susceptibility in many pathogenic organisms isolated in intensive care units. Antibiotic stewardship programs (ASPs) have been recommended as a strategy to reduce and delay the impact of AMR. A crucial step in ASPs is understanding antibiotic utilization practices and quantifying the problem of inappropriate antibiotic use to support a targeted solution. We aim to characterize antibiotic utilization and determine the appropriateness of antibiotic prescription in a tertiary care pediatric intensive care unit in Saudi Arabia.Methods A retrospective cohort study was conducted at King Abdullah Specialized Children’s Hospital (KASCH), Riyadh, Saudi Arabia, over a 6-month period. Days of therapy (DOT) and DOT per 1000 patient-days were used as measures of antibiotic consumption. The appropriateness of antibiotic use was assessed by two independent pediatric infectious disease physicians based on the guidelines of the Centers for Disease Control (CDC) 12-step campaign to prevent antimicrobial resistance among hospitalized children.Results During the study period, 497 patients were admitted to the PICU, accounting for 3009 patient-days. A total of 274 antibiotic courses were administered over 2553 antibiotic days. Ceftriaxone, vancomycin, ceftazidime, and cefazolin were responsible for the highest rates of consumption (164.8, 150.5, 91.7, and 83.1 DOTs per 1000 patient-days, respectively). Forty-eight percent of antibiotic courses were found to be nonadherent to at least 1 CDC step. The top reasons were inappropriate antibiotic choice (empirically or definitive) (31.3%) and inappropriate prophylaxis (30.2%). Infectious disease service consultation decreased the likelihood of inappropriate consumption of antibiotics.Conclusions Antibiotic consumption was high in our setting, with significant inappropriate utilization mainly due to empiric choices and the duration of prophylaxis. These data could inform decision-making in antimicrobial stewardship programs and strategies. The CDC steps provide a more objective tool and limit biases when assessing antibiotic appropriateness.