ObjectiveTo establish the clinical relevance of drug interactions between nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensives, based on the interaction severity and probability of occurrence. DesignSystematic review. Data sourcesA PubMed/Medline search was made using the MeSH terms: NSAIDs, Antihypertensive drugs, and Drug interactions. Data extractionArticles between 2002 and 2012, human studies, in Spanish and English and full text access were included. Found articles were included and some of the references used in this works. Studies with in vitro methods, effects on ocular hypertension and those who do not consider the interaction NSAIDs, antihypertensives were excluded. For the selection of the papers included three independent reviewers were involved. We used a tool for data extraction and for assess of the interaction clinical relevance. ResultsNineteen of 50 papers found were included. There were identified 21 interactions with pharmacodynamic mechanism, classified by their clinical relevance in level-2 high risk (76.2%) and level-3 medium risk (23.8%). In addition, evidence of 16 combinations of no interaction were found. ConclusionsSome NSAIDs may attenuate the effectiveness of antihypertensive drugs when used concurrently, especially with angiotensin converting enzyme inhibitors, diuretics, beta blockers and angiotensin receptorsii blockers. There was no evidence of effect modification of calcium channel antagonists, especially dihydropyridine, by concurrent use of NSAIDs.