A randomized, double-blind, placebo-controlled, parallel-group, multicenter, 8-week trial (with subsequent open-label phase) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy (DPN). For enrollment, patients must have had at baseline: 1- to 5-year history of DPN pain; pain score > or =40 mm (Short-Form McGill Pain Questionnaire [SF-MPQ] visual analogue scale); average daily pain score of > or =4 (11-point numerical pain rating scale [0 = no pain, 10 = worst possible pain]). One hundred forty-six (146) patients were randomized to receive placebo (n = 70) or pregabalin 300 mg/day (n = 76). Primary efficacy measure was endpoint mean pain score from daily patient diaries (11-point numerical pain rating scale). Secondary measures included SF-MPQ scores; sleep interference scores; Patient and Clinical Global Impression of Change (PGIC and CGIC); Short Form-36 (SF-36) Health Survey scores; and Profile of Mood States (POMS) scores. Safety assessment included incidence and intensity of adverse events, physical and neurological examinations, and laboratory evaluations. Pregabalin produced significant improvements versus placebo for mean pain scores (P < 0.0001); mean sleep interference scores SF-36 Bodily Pain subscale (P < 0.0001); total SF-MPQ score (P < 0.01); SF-36 Bodily Pain subscale (P < 0.03); PGIC (P = 0.001); and Total Mood Disturbance and Tension-Anxiety components of POMS (P < 0.03). Pain relief and improved sleep began during week 1 and remained significant throughout the study (P < 0.01). Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo. Most adverse events were mild to moderate and did not result in withdrawal. Pregabalin was safe and effective in decreasing pain associated with DPN, and also improved mood, sleep disturbance, and quality of life.