Borderline personality disorder is a common and severe psychiatric illness. The goal of this study was to determine whether topiramate can influence patients' borderline psychopathology, health-related quality of life, and interpersonal problems. Women meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Structured Clinical Interview II criteria for borderline personality disorder were randomly assigned in a 1:1 ratio to topiramate titrated from 25 to 200 mg/d (n = 28) or placebo (n = 28) for 10 weeks. Primary outcome measures were changes on the Symptom-Checklist, on the SF-36 Health Survey, and on the Inventory of Interpersonal Problems. Body weight and additional side effects were assessed weekly. According to the intent-to-treat principle, significant changes (all P < 0.001) on the somatization, interpersonal sensitivity, anxiety, hostility, phobic anxiety, and Global Severity Index scales of the Symptom Checklist were observed in the topiramate-treated subjects after 10 weeks (no significant changes on the obsessive-compulsive, depression, paranoid ideation, and psychoticism scales). In the SF-36 Health Survey, significant differences were observed on all 8 scales (all P < 0.01 or P < 0.001). In the Inventory of Interpersonal Problems, significant differences (all P < 0.001) were found in the scales for overly autocratic, overly competitive, overly introverted, and overly expressive (no significant differences in the scales for overly cold, overly subassertive/subservient, overly exploitable/compliant, and overly nurturant/friendly). Weight loss was additionally observed (p < 0.001). Topiramate appears to be a safe and effective agent in the treatment in women with borderline personality disorder. Additional weight loss can be expected.