OBJECTIVES: Several studies establish that the use of antidepressants associated with an increased risk of myocardial infarction (MI). However, available evidence on tricyclic antidepressants (TCAs) is conflicting. We therefore examined the association between TCAs use and risk of MI by conducting a detailed systematic review and meta-analysis using all observational studies published regarding this subject. METHODS: A PubMed/MEDLINE search was conducted for studies published up to 31^stDecember, 2013. The studies were first evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects model if heterogeneity presents or otherwise fixed-effects model. Cumulative meta-analysis, subgroup and sensitivity analyses were also performed. RESULTS: Six (3 cohort and 3 case-control) studies satisfying the inclusion criteria were considered for this study. There was heterogeneity among the studies (p_{heterogeneity} <0.001, I = 98%) but no publication bias (Begg’s p = 0.70 and Egger’s p = 0.45). We observed no association between TCAs use and risk of MI (RR 1.14, 95% CI 0.67-1.96, p =