Aspirin reduces the secondary incidence of myocardial infarction and vascular death, but some people on aspirin sustain a subsequent vascular event, suggesting the phenomenon of aspirin resistance. Based on epidemiologic data, some people have recommended avoiding ibuprofen in patients taking aspirin and suggested that ibuprofen reverses the cardioprotection offered by aspirin. We review the related literature. Although the interaction between aspirin and ibuprofen is pharmacologically plausible as shown by in vivo studies, the clinical implications of this observation are unknown. There are no randomized, controlled trials addressing this particular issue. The data obtained from observational and epidemiologic studies is scanty, conflicting, and limited. Therefore, the advice to avoid ibuprofen in patients taking aspirin to avoid the reversal of cardioprotection offered by aspirin seems premature.