Background: This was a 6-week, randomized, double-blind, multicenter study evaluating the efficacy of pregabalin in the treatment of painful diabetic neuropathy. Materials and Methods: Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin (150 or 600 mg/day by mouth) or placebo. The primary efficacy variable was mean pain score at the end of treatment. Results: Efficacy results indicate that pregabalin 600 mg/day significantly decreased mean pain score to 4.3 (vs 5.6 for placebo, P _ .0002) and increased the proportion of patients who had a >50% decrease from baseline pain (39% vs 15% for placebo, P _ .002). Pregabalin also significantly reduced sleep interference, past week and present pain intensity, sensory and affective pain scores, and bodily pain and decreased by >50% the number of patients describing their pain as gnawing, sickening, fearful, and punishing–cruel. More patients receiving pregabalin 600 mg/day than placebo showed improvement, as rated on the Clinical and Patient Global Impression of Change scales, 73% vs 45% and 85% vs 47%, respectively. Pregabalin 150 mg/day was essentially no different from placebo. Dizziness was the most common side effect. Conclusion: These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy.