Post hoc analyses of pregabalin RCTs suggest rapid onset of pain relief. This double-blind, randomized, placebo-controlled trial of pregabalin in patients with PHN prospectively evaluated time to onset of meaningful pain relief. Clinically meaningful pain relief was defined as ≥1-point improvement in daily pain score (using an 11-point NRS recorded in electronic daily diaries) followed by a decrease of ≥30% in weekly pain score at endpoint. Patients with PHN pain ≥3 months, pain VAS score ≥40 mm (100-mm scale), and who completed the daily pain NRS at least 4 times (average daily score ≥4) during the 7-day screening period were eligible. Patients were allowed to continue on stable (≥30 days) treatment regimens for their pain. Ninety-one patients were randomized to flexible-dosage pregabalin (dosage optimized for efficacy/tolerability to 150, 300, or 600 mg/d, BID); 88 to 300-mg/d fixed-dosage pregabalin; and 90 to placebo for 4 weeks of treatment. Primary efficacy parameter was time to onset of clinically meaningful pain relief, summarized with Kaplan-Meier plots and tested for treatment differences using a Cox model controlling for study site and baseline pain score. Most patients (56%) were male; mean age=67.4 years (range, 40-86); mean PHN duration =2.5 years; baseline mean pain score=6.3-6.7. Eighty-six flexible-dosage patients (94.5%), 70 fixed-dosage patients (79.5%), and 75 placebo patients (83.3%) completed the trial. Median time to meaningful pain relief: flexible-dosage pregabalin, 3.5 days (P<.0001 vs placebo); fixed-dosage, 1.5 days (P<.0001). Less than half of placebo patients achieved ≥30% response, so median time to meaningful pain relief is at least greater than the study observation period. Pregabalin was generally well-tolerated. Most common treatment-related AEs: dizziness (flexible-dosage, 24%; fixed-dosage, 28%; placebo, 7%) and somnolence (11%, 18%, 2%). Pregabalin demonstrated rapid onset of clinically meaningful and sustained pain relief, with median time to onset of 1.5 days in the fixed-dosage group.