Colchicine has demonstrated promising effects in inhibiting local and systemic inflammation during acute coronary syndrome (ACS). However, the efficacy of colchicine in ACS is controversial. We performed a meta-analysis to assess the utility of colchicine in ACS by systematically searching randomized controlled trials. Recurrent myocardial infarction, coronary revascularization, and stroke were included as efficacy endpoint parameters whereas safety endpoints chosen were all-cause mortality, cardiovascular mortality, infectious events, and gastrointestinal (GI) adverse events. Nine identified studies were included (n = 7207 participants). Colchicine may reduce the risk of coronary revascularization by 54% [relative risk (RR) 0.46, 95% confidence interval (CI) 0.29–0.73; P < 0.01] and stroke by 61% (RR 0.39, 95%CI 0.18–0.81; P = 0.01). We observed no significant difference in all-cause mortality (RR 1.25, 95%CI 0.70–2.24; P = 0.46), cardiovascular mortality (RR 0.99, 95%CI 0.58–1.69; P = 0.98), recurrent myocardial infarction (RR 0.75, 95%CI 0.49–1.14; P = 0.18), and infectious events (RR 0.67, 95%CI 0.08–5.52; P = 0.71). Colchicine increased the risk of GI adverse reactions (RR 1.89, 95%CI 1.25–2.84; P < 0.01). Subgroup analysis of loading doses did not reveal significant differences in all endpoints (all P > 0.05), whereas subgroup analysis of follow-up periods showed a lower risk of GI adverse reactions with longer follow-up (P < 0.01), which may be related to establishing tolerability. Trial sequential analysis suggested that further data are needed before definitive conclusions can be drawn. Colchicine may decrease the occurrence of stroke and revascularization in ACS, whereas slightly increasing the risk of GI reactions. The loading doses probably did not significantly improve the prognosis of patients.