Aim: This study examined the efficacy and the safety of peanut oral immunotherapy (OIT). Methods: We recruited 60 patients aged six years to 18 years who had a moderate-tosevere reaction to a double-blind placebo-controlled peanut challenge: 39 received OIT during an eight-month build-up phase and maintenance phase and 21 controls avoided peanuts. We measured specific immunoglobulin E and G4 (IgE and IgG4) to peanuts and to Ara h 1, 2, 3, 8 and 9 and monitored adverse events, bronchial hyper-responsiveness (BHR) to methacholine and fractional concentrations of exhaled nitric oxide (FeNO). The median follow-up period was 30 months. Results: Most (85%) of the OIT patients passed the build-up phase and 67% tolerated 5 g of peanuts during the post-treatment challenge. No controls were desensitised, with a risk ratio of 29 and 95% confidence interval of 1.9-455. During OIT, IgE to peanut, Ara h 1, 2 and 3 decreased and IgG4 increased. Consuming peanuts had no harmful effects on BHR or FeNO. The annual incidence rate of emergency visits during the follow-up period was 11% or 3.0 per 10 000 patient-days. Conclusion: Peanut OIT was efficacious in severe allergies without negative effects on airway inflammation, but unpredictable long-term reactions might occur.