Introduction: Anti-inflammatory therapies have been increasingly investigated for the reduction of cardiovascular (CV) events. The goal of this study was to summarize and compare the relative effectiveness of anti-inflammatory medications for the reduction of CV events in a systematic review and network-meta-analysis. Methods: In our systematic review, we included studies from Medline, Embase, the Cochrane Central Register of Controlled Trials, as well as clinical trial registry websites, Europe PMC, and conference abstract hand-searching. Randomized controlled trials were selected for inclusion if they included at least one anti-inflammatory treatment and involved patients with CAD. Bayesian network meta-analyses was performed to calculate risk estimates using random effects analyses in patients with ACS as well as stable CAD for the reduction of MACE. Results: A total of 14,699 studies were screened; sixty-one articles, all randomized control trials, met eligibility criteria for inclusion. A total of 41,647 patients were included in the stable CAD network analysis and 29,388 patients were included in the ACS network analysis. In the ACS analysis, both non-steroidal anti-inflammatory (NSAID) use (OR: 0.30, 95% Credible Limits [CrI]: 0.11-0.74) and colchicine use were associated with a significant reduction in MACE compared to control (OR: 0.71, 95% Credible Limits [CrI]: 0.58-0.88). In the stable CAD analysis, both corticosteroids (OR: 0.44, 95% CrI: 0.26-0.73) and colchicine (OR: 0.65, 95% Credible Limits [CrI]: 0.54-0.77) were associated with a significant reduction in MACE compared to control. Conclusions: In patients with acute coronary syndromes, NSAIDs and colchicine were associated with a reduction in the risk of major adverse cardiac events. In patients with stable coronary artery disease, both colchicine and steroids were associated with a reduction in the risk of major adverse cardiac events. For a comprehensive analysis of benefits and harms of anti-inflammatory therapies, large comparative studies or network meta-regression analyses of patient-level data will be required. Systematic review registration number: PROSPERO registry—CRD4202230328