BACKGROUND Glutathione-S-transferase (GST) enzymes play a role in scavenging endogenous oxidants. Altered enzyme activity results from inherited polymorphisms, which results in increased oxidative stress. This study explores the role of GST polymorphisms as modifiers of surgical complications in patients undergoing head and neck microvascular reconstruction. METHODS Patients newly diagnosed as having head and neck cancer and undergoing microvascular reconstruction were selected. Polymerase chain reaction was used to determine GST genotypes. Demographic factors, treatment, and postoperative complications were reviewed. Multivariate logistic regression analysis was used to estimate the risk of surgical complications associated with variant genotypes. RESULTS A total of 107 patients were evaluated. Surgical and medical complication rates were 44.9% and 25.2%, respectively. The variant Val allele at the GSTP1 105 codon was associated with a significantly increased risk of surgical complications (P = .046; adjusted relative risk, 1.7; 95% confidence interval, 1.1-2.6). There was no significant association between the other GST variant genotypes and surgical complications. No association was noted between variant GST genotypes and the risk of medical complications. CONCLUSIONS GSTP1 codon 105 polymorphism may be a marker for risk of wound complications in head and neck microvascular reconstruction.