We aimed to evaluate the efficacy of tricyclic antidepressants (TCAs) as a therapeutic option for irritable bowel syndrome (IBS) through meta-analysis of randomized controlled trials. For the years 1966 until September 2008, PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for double-blind, placebo-controlled trials investigating the efficacy of TCAs in the management of IBS. Seven randomized, placebo-controlled clinical trials met our criteria and were included in the meta-analysis. TCAs used in the treatment arm of these trials included amitriptyline, imipramine, desipramine, doxepin and trimipramine. The pooled relative risk for clinical improvement with TCA therapy was 1.93 (95% CI: 1.44 to 2.6, P < 0.0001). Effect size of TCAs versus placebo for mean change in abdominal pain score among the two studies was -44.15 (95% CI: -53.27 to -35.04, P < 0.0001). It is concluded that low dose TCAs exhibit clinically and statistically significant control of IBS symptoms.