Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have emerged as potential chemopreventive agents for melanoma. However, the clinical studies have provided contradictory results as to whether NSAIDs reduce the risk of melanoma. Our aim was to assess this association through a detailed meta-analysis of the studies on the subject published in the peer-reviewed literature. Relevant studies were identified by searching PubMed, EMBASE and Web of Science electronic databases up to July 2012. Reference lists from retrieved articles were also reviewed. Pooled relative risk (RR) estimates and corresponding 95% confidence intervals (CIs) were calculated using the fixed-effects or the random-effects models on the basis of heterogeneity analysis. Subgroup analyses were carried out where data were available. Ten studies involving 490 322 participants contributed to the meta-analysis. The summary RR estimate on the basis of all studies did not indicate that overall NSAIDs use significantly decreases the risk of melanoma (RR=0.94; 95% CI, 0.86-1.03). The use of neither aspirin (RR=0.96; 95% CI, 0.89-1.03) nor nonaspirin NSAIDs (RR=1.05; 95% CI, 0.96-1.14) was associated with the risk of melanoma. Similar results were obtained in the subgroup analyses of cohort studies (RR=1.03; 95% CI, 0.95-1.13), high-intensity NSAID use (the highest dose of NSAID use reported by included studies, RR=1.05; 95% CI, 0.79-1.40), and long-term NSAID use (longest duration of NSAID use reported by included studies, RR=0.87; 95% CI, 0.66-1.14). However, a slight reduction in the risk of melanoma by taking NSAIDs was observed in case-control studies (RR=0.86; 95% CI, 0.80-0.93). In conclusion, the results of our meta-analysis did not indicate that the use of NSAIDs or aspirin is associated with the risk of melanoma. More and in-depth research should focus on those problems in the future.