The outcomes and clinical toxicity profile associated with the use of pencil beam scanning proton therapy (PBS-PT) in pediatric patients are not well characterized. We provide the first report of systematically characterization of pediatric patients treated with PBS-PT. Between 2017 and 2020, 694 patients with childhood cancer were enrolled on a single institution phase IV trial and treated with PBS-PT. Outcomes were recorded at protocol-scheduled clinical evaluations and augmented with medical record review and nDepth natural language processing. Toxicities were graded as per Common Terminology Criteria for Adverse Events (CTCAE v4.0). All records were reviewed for treatment modality, initial vs. retreatment setting, treatment type, and time to complication or treatment failure. Failure events were categorized as local, regional and/or distant according to disease protocol standards. Cumulative incidence was estimated using the cmprsk package in Rstudio v.1.2.5033. With a median follow-up of 2.1 years (IQR 2.57-3.44), 694 patients were treated with PBS-PT as a first (N = 506), or subsequent course (N = 49) for both CNS (N = 491, 71%) and non-CNS (solid-tumor, leukemia, lymphoma) (N = 193, 28%) diagnoses. Disease progression occurred in 127 patients with an event-free survival at 2 years of 70% (95% CI 65.6-75.6). The cumulative incidence of local, regional and distant failure at 2 years was 8.9%, 0.67%, and 17.2%, respectively. Overall survival was 83.8% (95% CI 79.9-88.0) at 2 years for the entire cohort. The cumulative incidence at 2 years of ≥ grade 3 (severe, life-threatening or disabling) toxicity was 18.7%. The incidence by treated site was CNS 18.0%, head/neck 10.7%, chest 8.5%, abdomen 7.2%, and pelvis 11.1%. The most common CNS complications were necrosis and hearing impairment while the most common non-CNS complications were weight loss, vomiting, and radiation dermatitis. The rate of hospitalization due to a PBS-PT attributable toxicity was 6.0% at 2 years. Among survivors treated with CNS irradiation, the cumulative incidence of ≥ grade 3 CNS necrosis, CNS vasculopathy, and permanent neurologic deficit was 2.6%, 0.7%, and 4.9%, respectively, at 2 years. The cumulative incidence of fracture and osteoradionecrosis was 0.55% and 0.58%, respectively, at 2 years. Pediatric patients treated with PBS-PT have favorable survival and low toxicity rates, but one in five may still experience transient severe, disabling or life-threatening toxicity. This experience defines a unique group of pediatric patients who undergo protocol-directed follow-up at a single institution. These results will serve as a benchmark for the assessment and verification of clinically significant complications in both historic photon treated cohorts and future prospective clinical trials utilizing proton therapy.