Background: Oral immunotherapy (OIT) has shown promise for peanut-allergic preschool children. Studies report it is safe and effective, with over 70% achieving sustained unresponsiveness. Knowledge about preschool OIT for other allergens and multiple food allergies is still limited. Objective: To assess the safety of a pragmatic OIT protocol in preschool children with single and multiple food allergies. Methods: This single-center prospective intervention study included children aged 9-24 months with proven food allergy (sensitization and a positive oral food challenge (OFC)). After a short dose escalation phase, children received one year of low-dose (300 mg protein/day) OIT, followed by an exit OFC four weeks after stopping therapy. Children with multiple food allergies received OIT for up to four allergens. Allergic dosing reactions (ADR) were recorded and classified using Sampson’s severity score (grades I-V). Results: Between May 2019 and Oct 2022, 124 children (median age 17, IQR 11-20 months) started OIT for 189 allergies. Peanut (n=52), cashew (n=46) and egg (n=38) allergies were the most common. ADR occurred in 89 children and 117 OIT trajectories, most frequently during dose escalation (65%). Reactions (95.3%) were mild (grade I-II) and mostly resolved spontaneously (55.6%) or with antihistamines (29.9%). Ten reactions were severe (grade III-IV). Reaction severity did not differ between single and multiple OIT or among the different allergens. Ten trajectories were discontinued due to side effects. Conclusions: OIT for various allergens and multiple food allergies appears safe for preschoolers. Side effects are common but typically mild. However, they may lead to therapy discontinuation.