This open-label study evaluated the long-term safety of pregabalin for treatment of chronic pain associated with diabetic peripheral neuropathy (DPN), postherpetic neuralgia (PHN), and fibromyalgia syndrome (FMS). Patients must have previously participated in a pregabalin clinical trial, and enrollees were required to have failed treatment for their pain with a TCA (≥75 mg/day), gabapentin (≥1800 mg/day), and ≥1 third-line treatment. Patients were allowed to continue concomitant medications. Patients received pregabalin 150-600 mg/d adjusted to optimize efficacy and tolerability. The SF-MPQ was administered at baseline and at each quarterly visit. 45, 36, and 25 patients with DPN, PHN, and FMS were enrolled. Baseline mean VAS pain score was 73.5 mm, with little variance by disease state. During the study′s first 15 months, patients were required to take 4 ″drug holidays″ of 3-28 days at the end of quarters 1-4 to verify the pain-relief benefit of pregabalin (interim results describing these first 15 months have been reported previously). 76% of patients received pregabalin for ≥24 weeks, 74% for ≥52 weeks, 67% for ≥104 weeks, 62% for ≥156 weeks, and 28% for ≥182 weeks. The most frequently used dosage was 600 mg/d (122 patient years). Change from baseline to endpoint in mean VAS pain score was –26.3 mm (SD=28.56). The most frequent treatment-associated AEs—in ≥10% of patients—were dizziness (18%), somnolence (18%), and peripheral edema (11%). 10% of patients discontinued because of associated AEs. 3 patients died during the study; no deaths were associated with treatment. Pregabalin was safe and generally well tolerated in this long-term study, which encompassed 256 patient-years. The AE profile observed in this study was similar to that reported in the literature from short-term trials. In these patients who had previously failed multiple treatments for DPN, PHN, or FMS, pregabalin was associated with improvements in mean pain scores.