The aim of the study was to evaluate the risks of hospitalisation and death due to hypersensitivity reactions associated with the NSAIDs naproxen and ibuprofen, using a record-linkage database for Tayside, Scotland (population 400,000). Cohorts of patients exposed to naproxen (n=54,038) and ibuprofen (n=79,513) were assembled. There were no deaths due to hypersensitivity. There was an increased risk of unvalidated hypersensitivity reactions during periods on-drug versus off-drug in patients exposed to naproxen and ibuprofen. However, after checking medical records, none of the three valid cases of hypersensitivity in the naproxen cohort and neither of the two in the ibuprofen cohort were judged to be due to NSAID exposure. A "worst-case" scenario gave an adjusted rate-ratio of on-drug with naproxen versus on-drug with ibuprofen of 1.63 (0.50, 5.29). The study shows that hypersensitivity reactions associated with NSAID use are rare, and provides no evidence that the risks of hypersensitivity reactions differ between naproxen and ibuprofen.