The diagnosis of food allergy is challenging due to different immunologic mechanisms and diversity of symptoms. An open or double-blinded oral food challenge (OFC) was performed on 391 children (aged 0.2-16.9 years) with suspected cow's milk (n = 266) or wheat allergy (n = 125) to characterize immediate, delayed, and transient symptoms, and to evaluate the role of earlier food-related symptoms and immunoglobulin E (IgE)-[pmediated sensitization for the OFC outcome. The OFC resulted in an immediate positive reaction in 38% (n = 148) and a delayed positive reaction in 21% (n = 81) of the 391 children. Transient reactions, the majority of which were localized skin reactions, were seen in almost third (n = 50) of the patients with a negative OFC result (n = 162/391). Immediate localized skin reactions were more common during the milk challenge (p = 0.010), whereas immediate lower respiratory tract symptoms (p = 0.001) were more common during the wheat challenge. Although 14% (n = 21) of those with an immediate reaction received i.m. adrenalin as a treatment of the reaction, there were no life-threatening events. Multivariate analyses revealed that independent risk factors for the immediate OFC outcome were earlier moderate-to-severe immediate food-related reactions, marked IgE-mediated sensitization to the suspected food, and in case of wheat, age <12 months. The accuracy of OFCs can be enhanced without increasing the risk of serious allergic reactions by taking into account earlier food-related symptoms and the level of IgE-mediated sensitization, by refining our knowledge of transient nonspecific reactions, and by applying standardized OFC protocols with over-one-day challenges.