Objective. To describe leflunomide (LEF) use in a national cohort of 3,325 veterans. Methods. Prescriptions for LEF and 9 disease-modifying antirheumatic drugs written between October 1998 and June 2001 at all Veterans Affairs (VA) medical centers were obtained from VA national databases. Results. LEF was initiated with a loading dose of 100 mg daily for 3 days in 61% of patients, and 42% of patients discontinued LEF. LEF was more likely to be discontinued if a 3-day 100-mg loading dose was prescribed, patients were younger than 44 years or older than 75 years, or reported an annual family income <$60,000. Review of medical records of 291 discontinuers revealed that the most common reasons for discontinuation were inefficacy (30%), gastrointestinal symptoms (29%), medication noncompliance or lost to followup (14%), and elevated liver enzymes (5%). Conclusion. LEF is relatively safe in clinical practice. The VA's national databases provide an excellent, inexpensive resource for postmarketing evaluation of rheumatologic medications.