Buffered lidocaine has been shown to be less painful than plain lidocaine for anesthetizing wounds. However, the effect of a buffering agent on the local host defenses has not been evaluated. The infection rates of wounds anesthetized with plain lidocaine versus buffered lidocaine were compared in an observational cohort study. Consecutive emergency department patients with traumatic wounds that required sutures had a closed-question wound registry sheet prospectively completed. Follow-up data were obtained at the time of the return visit. Patients failing to return were contacted by telephone. Data were analyzed for wound infection rates comparing plain lidocaine with buffered lidocaine. Chi-squared or Fisher exact tests were used for statistical analysis. Of 2,711 patients analyzed, 2,279 had received plain and 432 had received buffered lidocaine. The infection rate for patients treated with plain lidocaine was 3.5%, versus that for patients treated with buffered lidocaine, 3.9% (P = .63). After adjustment for confounding variables, the infection rate did not differ between plain and buffered lidocaine. The infection rates of wounds repaired after anesthesia with either plain or buffered lidocaine are similar.