Background: Proton-pump inhibitors (PPI) are frequently used in the emergency and general practice settings in several clinical presentations linked to acute upper gastro-intestinal tract disorders as abdominal or chest pain without recommendations. Objective: The aim of this scoping review was to assess pain reduction, diagnostic performance, and safety in the first 24 h-management in primary care or emergency medicine. Methods: Search was realized by 2 independent reviewers in PubMed, Embase, and Web of Science following PRISMA-ScR guidelines. Only original articles or systematic reviews in English were included. Studies about chronic and/or bleeding conditions, therapeutic cocktails and studies without pain evaluation were excluded. Two methodologies were used for bias estimation. Results: From 4442 titles, 79 full-text articles were assessed, and 9 were included. There is no strong evidence supporting the use of PPI as a first line analgesic or diagnostic test in acute syndromes linked to acute upper gastro-intestinal tract disorder. A small effect in pain reduction was retrieved in patients with low pain scores. A poor additional value in patients with gastric reflux, and a low specificity compared to other diagnostic tests were observed. A short-term PPI administration appears to be safe with low risk of serious allergic reactions, and poor adverse effects (moderate evidence). Conclusion: Although PPIs may contribute to the multimodal analgesia in acute settings, with few and/or minor side effects, no recommendation can be drawn for their use as a primary analgesic. Data regarding the relevance of the PPI test are much less clear, no data regarding care pathways are available.