This study conducted a network meta-analysis to evaluate the cardiovascular safety of seven non-steroidal anti-inflammatory drugs (NSAIDs) compared to placebo. The analysis included 31 trials with over 116,429 patients and more than 115,000 patient-years of follow-up. The primary outcome was myocardial infarction, with secondary outcomes including stroke, cardiovascular death, and death from any cause. Rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with 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 showed the least harm. The study concluded that while naproxen appeared to be the safest option, the safety profiles of individual drugs varied significantly, and the estimated rate ratios for comparisons with placebo were generally imprecise. The findings highlight the need to consider cardiovascular risk when prescribing any NSAID.This study conducted a network meta-analysis to evaluate the cardiovascular safety of seven non-steroidal anti-inflammatory drugs (NSAIDs) compared to placebo. The analysis included 31 trials with over 116,429 patients and more than 115,000 patient-years of follow-up. The primary outcome was myocardial infarction, with secondary outcomes including stroke, cardiovascular death, and death from any cause. Rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with 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 showed the least harm. The study concluded that while naproxen appeared to be the safest option, the safety profiles of individual drugs varied significantly, and the estimated rate ratios for comparisons with placebo were generally imprecise. The findings highlight the need to consider cardiovascular risk when prescribing any NSAID.