Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for the treatment of painful musculoskeletal conditions. When prescribing oral NSAIDs, clinicians must consider coexisting cardiovascular, cerebrovascular, gastrointestinal, and renal disease because oral NSAIDs are associated with a broad spectrum of adverse effects on these systems. The different safety profiles of NSAIDs can be attributed to differences in the extent to which the drug inhibits cyclo-oxygenase-1 vs -2 and their potential for drug-drug interactions. This narrative review intends to guide the clinician in prescribing oral NSAIDs while taking into consideration these comorbid conditions and drug interactions. LEVEL OF EVIDENCE: III.
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