Objective: We assessed the efficacy of colchicine in COVID-19 patients through a systematic review. Methods: Six databases were searched until March 2022 for studies assessing colchicine versus control in hospitalized patients with COVID-19. The primary outcome was mortality, and secondary outcome was length of hospitalization. Inverse variance and random effect meta-analyses were performed. The strength of evidence was assessed using GRADE. Results: Nine studies (five randomized clinical trials (RCTs) and four non-randomized studies of intervention (NRSI); n = 13,478). Colchicine did not reduce mortality in comparison with the standard of care in RCTs (RR 0.99; 95%CI 0.90 to 1.10; p = 0.90); however, it did reduce mortality in NRSI studies (RR 0.45; 95%CI 0.26 to 0.77; p = 0.02). In the analysis of RCTs, colchicine did not reduce the length of hospitalization in comparison with the standard of care (MD: −2.25 days; 95%CI: −9.34 to 4.84; p = 0.15). Most studies were scored as having a high risk of bias. Quality of evidence was very low for primary and secondary outcomes. Conclusion: Colchicine did not reduce the mortality and length of hospitalization in comparison with the standard of care in hospitalized patients with COVID-19. The published evidence is insufficient and of very low quality to recommend treatment in patients with COVID-19.