This study compared the efficacy of topical lidocaine patches versus vehicle (placebo) patches applied directly to the painful skin of subjects with postherpetic neuralgia (PHN) utilizing an `enriched enrollment' study design. All subjects had been successfully treated with topical lidocaine patches on a regular basis for at least 1 month prior to study enrollment. Subjects were enrolled in a randomized, two-treatment period, vehicle-controlled, cross-over study. The primary efficacy variable was `time to exit'; subjects were allowed to exit either treatment period if their pain relief score decreased by 2 or more categories on a 6-item Pain Relief Scale for any 2 consecutive days. The median time to exit with the lidocaine patch phase was greater than 14 days, whereas the vehicle patch exit time was 3.8 days (P<0.001). At study completion, 25/32 (78.1%) of subjects preferred the lidocaine patch treatment phase as compared with 3/32 (9.4%) the placebo patch phase (P<0.001). No statistical difference was noted between the active and placebo treatments with regards to side effects. Thus, topical lidocaine patch provides significantly more pain relief for PHN than does a vehicle patch. Topical lidocaine patch is a novel therapy for PHN that is effective, does not cause systemic side effects, and is simple to use.