Abstract Purpose The aim of the study was to compare the cost-effectiveness of different imaging strategies for the diagnosis of pediatric intussusception using a decision analytic model. Methods A Markov decision model was constructed to model effects of radiation exposure at the time of intussusception in a hypothetical cohort of 2-year-old children. The 2 strategies compared were ultrasound followed conditionally by contrast enema (US/CE) vs contrast enema (CE) alone. The model simulated short-term and long-term outcomes of the patients, calculating the average quality-adjusted life years (QALYs) and health care costs associated with each arm. Results The use of ultrasound as a first-line diagnostic modality would result in a decrease of 79.3 and 59.7 cases of radiation-induced malignancy per 100,000 male and female children evaluated, respectively. For male and female children with intussusception, US/CE was both the most costly initial imaging strategy and the most effective compared with CE. The incremental cost-effectiveness ratios of US/CE to CE was $70,100 (boy) and $92,227 (girl) per quality-adjusted life years gained. Conclusions In a Markov decision model of pediatric acute intussusception, initial US/CE was both the most costly and the most effective strategy.