Background: Post-cardiac procedure atrial fibrillation (PCP-AF) is a significant medical problem. Inflammation is one of the key factors in the pathogenesis of PCP-AF. As a classical anti-inflammatory drug, colchicine may prevent the occurrence of PCP-AF. This meta-analysis of 12 randomized controlled trials (RCTs) analyzed the feasibility and safety of colchicine for the prevention of PCP-AF. Methods: PubMed, EMBASE, Web of Science, the Cochrane Library, and Google Scholar were retrieved for RCTs on the efficacy of colchicine in preventing atrial fibrillation. The primary endpoint was the diagnosis of PCP-AF, which includes cardiac surgery or pulmonary vein isolation. Evaluation was performed with estimated odds ratios (OR) and 95% confidence intervals (CI). Results: In this meta-analysis, 12 RCTs were selected and a total of 2297 patients were included. Colchicine therapy was associated with a reduced incidence of PCP-AF both in post-cardiac surgery (OR: 0.62; 95% CI: 0.49–0.78, p 0.0001, I{}^2 = 0%), and in post-pulmonary vein isolation (OR: 0.43; 95% CI: 0.30–0.62, p 0.0001, I{}^2 = 0%). Colchicine therapy was associated with increased side effects (OR: 2.81; 95% CI: 1.96–4.03, p 0.00001, I{}^2 = 26%). Conclusion: Colchicine can effectively prevent post-cardiac operative atrial fibrillation and relapse of atrial fibrillation after pulmonary vein isolation (PVI). However, colchicine can also increase the incidence of side effects, mainly gastrointestinal adverse events. More studies are needed to find a more appropriate treatment dose and time.