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There are various etiologies of erectile dysfunction (ED), including endothelial dysfunction, atherosclerosis, and chronic inflammation. Aspirin has a protective role against endothelial dysfunction and atherosclerosis, whease all non-steroidal anti-inflammatory drugs (NSAIDs) are known for their anti-inflammatory properties. However, association between the use of aspirin or non-aspirin NSAIDs and ED is controversial. Therefore, we reviewed this relationship.We systematically reviewed the pathophysiology of ED, physiological effect of prostaglandins, pharmacological action of NSAIDs, and clinical and basic research studies that evaluated the effect of aspirin or non-aspirin NSAIDs on ED.The research studies that assessed association between aspirin or non-aspirin NSAIDs are limited, and only 12 articles have been published. One clinical and three basic studies have claimed that aspirin or non-aspirin NSAIDs are beneficial for ED by preserving nitric oxide synthase impairment or penile blood hypercoagulability. One basic and two clinical studies considered them as risk factors because they interfered with prostaglandin production. By contrast, four clinical studies showed irrelevant results after controlling various medical indications. In addition, the mechanical effect of aspirin or non-aspirin NSAIDs on the nitric oxide pathway is still controversial.The available research studies revealed that association between aspirin or non-aspirin NSAIDs and ED is controversial. Considering the high frequency of drug use, further clinical and basic investigations should be conducted to clarify their exact relationship.