The present study assessed drug use and the validity of self-reports of substance use among help-seeking veterans referred to a specialty clinic for the assessment of posttraumatic stress disorder (PTSD). Patients (n = 341) were asked to provide a urine sample for use in drug screening as part of an evaluation of PTSD. Self-reports of substance use were compared with same-day supervised urine samples for 317 patients who volunteered to participate in a drug screening. Results suggested that self-reports were generally quite valid. Only 8% of the cases involved patients not reporting substance use detected by urine screens. A total of 42% of the participants were identified as using drugs of abuse (excluding alcohol) through self-report and urine drug screens. Among participants using drugs, PTSD diagnosis was significantly associated with greater marijuana and depressant use as compared with stimulant (cocaine and amphetamines) use.