There is strong evidence for a genetic contribution to the pathogenesis of panic disorder, with the functional catechol-O-methyltransferase (COMT) val158met polymorphism having been suggested as a potential susceptibility factor. In the present study, a meta-analysis of six available case-control studies (557 patients with panic disorder and 763 healthy controls in total) on the role of the COMT val158met polymorphism in panic disorder was conducted in an attempt to reconcile previous conflicting results and to facilitate evaluation of the role of COMT gene variation in panic disorder. Overall, no significant association, but strong between-study heterogeneity, was discerned. Analysis of studies pooled by ancestry yielded a significant association of the COMT 158val allele with panic disorder in Caucasian samples and, conversely, a trend towards association of the COMT 158met allele with the disorder in Asian samples. Interestingly, stratification for gender as well as ethnicity revealed that association of the 158val allele in Caucasians and, reciprocally, the 158met allele in Asian samples was restricted to females. The present meta-analysis provides tentative support for the COMT val158met polymorphism as a possible risk factor for panic disorder, with differential effects in Caucasian and Asian populations, and suggests a female-specific effect. However, given the relatively small number of case-control studies presently available, several more association studies, preferably including a larger number of family-based studies, are warranted for conclusive evaluation of the COMT val158met polymorphism as a vulnerability factor in panic disorder.