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The authors conducted a meta-analysis of published studies to (a) evaluate the premise that a history of major depression is associated with failure to quit smoking and (b) identify factors that moderate the relationship between history of depression and cessation outcome. Fifteen studies met the selection requirements and were coded for various study methodology and treatment characteristics. DSTAT was used to calculate individual study effect sizes, determine the mean effect size across studies, and test for moderator effects. No differences in either short-term (≤ 3 months) or long-term abstinence rates (≥ 6 months) were observed between smokers positive versus negative for history of depression. Lifetime history of major depression does not appear to be an independent risk factor for cessation failure in smoking cessation treatment.