A total of 402 patients were enrolled at 52 centers in a randomized, double-blind, controlled study of NGX-4010 (trans-capsaicin, 8% w/w) patch for the treatment of postherpetic neuralgia (PHN). The treatment consisted of a single one-hour patch application of NGX-4010 or a low-concentration capsaicin control (trans-capsaicin, 0.04% w/w) applied to the area of the skin described as painful, following pretreatment with topical local anesthetic. Efficacy and safety were assessed over 12 weeks. Patients recorded on a daily diary their “average pain for the past 24 hours” using the 11-point Numeric Pain Rating Scale (NPRS). Inclusion criteria included pain ≥ 6 months after herpes zoster lesion healing and an average baseline pain score between 3 and 9 inclusive. The percent change in average NPRS score from baseline as compared to weeks 2 to 8 and weeks 2 to 12 were analyzed. During weeks 2 to 8, the NGX-4010 group (N=206) experienced a mean NPRS score reduction of 29.6% compared to 19.9% in the control group (N=196; p=0.001). During weeks 2 to 8, 42% of NGX-4010 subjects responded to treatment (≥ 30% reduction in mean NPRS scores) as compared to 32% in the control (p=0.034). At week 8, there was a 30.9% pain reduction in the NGX-4010 group and a 20.1% reduction in the control (p=0.0015). The reduction in pain was sustained through week 12 (NGX-4010 -31.4%, control -21.6%; p=0.01). Treatment was generally well tolerated with no significant safety issues identified. As expected transient local application site reactions including erythema and pain were common but were self-limited and generally mild to moderate in severity. This study demonstrates that a single, one-hour application of NGX-4010 is generally well tolerated and results in significant pain reduction that is maintained for up to 12 weeks in patients with PHN.