BackgroundCaffeine enhances the efficacy of non-opioid analgesics. Data on the cardiovascular health effects of caffeine intake are controversial, and studies on the cardiovascular effects of medical caffeine use are lacking.ObjectiveThe study aims to explore the cardiovascular effects of an ibuprofen/caffeine combination in comparison to ibuprofen alone.MethodsSecondary analysis of a previously reported bioequivalence study of a single dose of a fixed dose ibuprofen/caffeine combination (400/100 mg)vs. ibuprofen alone in a randomized, cross-over design in 36 healthy volunteers. Plasma catecholamines were analyzed to enhance mechanistic interpretation of the data.ResultsAfter exclusion of 10 protocol violators (pre-dosing intake of caffeine), vital signs were comparable over a 24-h period in the absence and presence of caffeine. Plasma catecholamine levels were also comparable.ConclusionThese data do not support the hypothesis that occasional intake of a small dose of caffeine as part of pain medication imposes a health risk due to vital sign changes. Based on the proven increase in efficacy, the addition of caffeine to non-opioid analgesics such as IBU has a favorable risk/benefit profile for occasional use.