BACKGROUND: Crohn’s disease is a chronic disorder in which sections of the gastrointestinal tract become inflamed and ulcerated through an abnormal immune response. Costly anti-TNF-α treatments are indicated only after other treatments have not worked. However, anti-TNF-α treatments have been proposed as first line therapy due to their effectiveness. OBJECTIVE: The primary objective was to assess the incremental cost-effectiveness of early intervention with anti-TNF-α treatment vs. conventional step-up strategy at improving the number of steroid-free remission weeks gained from public healthcare payer and societal perspectives. METHODS: A two-dimensional probabilistic microsimulation Markov model with seven health states was constructed for children with moderate to severe Crohn’s disease. Newly-diagnosed children with Crohn’s disease aged 4-17 years who received anti-TNF-α treatment and other concomitant treatments, such as steroids and immunomodulators, within the first three months of diagnosis were compared to children with newly-diagnosed Crohn’s disease who received standard care of steroids and/or immunomodulators with the possibility of anti-TNF-α treatment only after three months of diagnosis. The outcome measure was weeks in steroid-free remission. The time horizon was three years. A scenario analysis examined variation in costs of anti-TNF-α treatment. A North American multi-centre, observational study of children with Crohn’s disease provided input into clinical outcomes and health care resource use. To reduce selection bias, propensity score analysis was used. RESULT: From a public healthcare payer perspective, early intervention with anti-TNF-α treatment was more costly with an incremental cost of $31,112 (95% CI: 2,939, 91,715) and more effective with 11.3 more weeks in steroid-free remission (95% CI: 10.6, 11.6) compared to standard care, resulting in an incremental cost per steroid-free remission week gained of $2,756. From a societal perspective, the incremental cost per steroid-free remission week gained for early anti-TNF-α treatment was $2,968. CONCLUSION: While unknown, if a willingness-to-pay threshold was assumed to be $2,500 per week in steroid-free remission, early intervention with anti-TNF-α would not be cost-effective. However, there is considerable uncertainty in the incremental cost-effectiveness ratio and many patients escalate to anti-TNF-α eventually. Therefore, restrictive policies on anti-TNF-α treatment access for pediatric Crohn’s patients may want to be re-visited by decision makers.