Background: An oral food challenge (OFC) is required for diagnosing food allergies; however, uncertain reactions can impair the determination of when to stop the test. We aimed to determine the associations between immediately occurring mild allergic skin signs/laryngeal symptoms and positive OFC results. Methods: We retrospectively included children (aged 6 months to 15 years) who underwent open OFC for hen’s egg (HE), cow’s milk (CM), or wheat at a single centre between May 2012 and March 2020. Participants with mild skin signs or laryngeal symptoms at OFC initiation were classified as “skin” or “laryngeal” cases, respectively. Using logistic regression, the risk of positive OFC results, in a skin or laryngeal case, was assessed using univariate and multivariate analyses. Age, sex, total target dose, and serum levels of total and food-specific immunoglobulin E were used as covariates in prediction models. Results: In total, 2954, 1126, and 850 tests for HE, CM, and wheat, respectively, were included and comprised 115 (4%) and 25 (0.9%), 92 (9%) and 24 (2%), and 7 (1.3%) and 0 (0%) skin and laryngeal cases, respectively. Children with reactions to both HE and CM had a higher risk of a positive OFC than controls (odds ratio [95% confidence interval]: 4.6 [3.3–6.4], 2.9 [2.0–4.1] and 6.5 [3.0–10.9], 4.9 [2.2–10.9], respectively). Areas under the curves of prediction models ranged from 0.61 to 0.71. Conclusions: Uncertain reactions immediately after test initiation could not robustly predict OFC results, indicating the OFC could be continued under careful observation.