A network meta-analysis evaluated the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs). The study included 31 randomized controlled trials involving 116,429 patients with over 115,000 patient-years of follow-up. NSAIDs tested included naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, and placebo. The primary outcome was myocardial infarction, with secondary outcomes including stroke, cardiovascular death, and death from any cause. Rofecoxib showed the highest risk of myocardial infarction compared to placebo (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen had the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib and diclofenac were associated with the highest risk of cardiovascular death. Naproxen was found to be the least harmful among the tested NSAIDs. The study concluded that there is little evidence to suggest that any of the investigated drugs are safe in cardiovascular terms. Cardiovascular risk should be considered when prescribing NSAIDs. The analysis used a Bayesian random effects model and considered direct and indirect evidence to compare the drugs. The results showed that most NSAIDs had increased risks for cardiovascular events compared to placebo, with the exception of naproxen. The study highlighted the need for further research due to the limited number of events and the imprecision of the estimates. The findings suggest that while some NSAIDs may carry a higher cardiovascular risk, naproxen appears to be the safest option. The study also emphasized the importance of considering cardiovascular risk when prescribing NSAIDs, especially for patients with a higher risk of cardiovascular events.A network meta-analysis evaluated the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs). The study included 31 randomized controlled trials involving 116,429 patients with over 115,000 patient-years of follow-up. NSAIDs tested included naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, and placebo. The primary outcome was myocardial infarction, with secondary outcomes including stroke, cardiovascular death, and death from any cause. Rofecoxib showed the highest risk of myocardial infarction compared to placebo (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen had the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib and diclofenac were associated with the highest risk of cardiovascular death. Naproxen was found to be the least harmful among the tested NSAIDs. The study concluded that there is little evidence to suggest that any of the investigated drugs are safe in cardiovascular terms. Cardiovascular risk should be considered when prescribing NSAIDs. The analysis used a Bayesian random effects model and considered direct and indirect evidence to compare the drugs. The results showed that most NSAIDs had increased risks for cardiovascular events compared to placebo, with the exception of naproxen. The study highlighted the need for further research due to the limited number of events and the imprecision of the estimates. The findings suggest that while some NSAIDs may carry a higher cardiovascular risk, naproxen appears to be the safest option. The study also emphasized the importance of considering cardiovascular risk when prescribing NSAIDs, especially for patients with a higher risk of cardiovascular events.