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.