Background : Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the main causes of hypersensitivity to drugs in the pediatric population. Studies about the natural history of cross-intolerance reactions to NSAIDs are scarce. The aim of this study was to assess cross intolerance to NSAIDs over time in the pediatric population. Methods : Retrospective study in patients under 18 years old diagnosed with cross intolerance to NSAIDs by oral challenge test between 1999 and 2019. These patients were prospectively re-assessed in 2021-2022 by challenge with acetylsalicylic acid (ASA). Patient characteristics and potential factors that might have helped them develop tolerance to NSAIDs were analysed. Results : Between 1999 and 2019, 46 patients were diagnosed with cross intolerance to NSAIDs; of these, 19 were re-assessed at a second visit after a mean of 116 months from initial diagnosis. The NSAID most involved in reactions was ibuprofen. At Visit 2, it was observed that 15 (78.9%) patients tolerated ASA and other NSAIDs. Patients with atopy and who initially presented with asthma were more likely to maintain their diagnosis of cross intolerance to NSAIDs ( p=0.001 and p=0.035, respectively). On the contrary, most patients with initial angioedema developed tolerance over time ( p=0.035). Conclusion : Patients with cross intolerance to NSAIDs may develop tolerance to them over time. This tolerance might be determined both by the presence of atopy and the initial history of the patient.