Alcohol consumption during pregnancy may lead to permanent damage in the offspring, including fetal alcohol spectrum disorders (FASD), which have an estimated prevalence of 1-8% worldwide. In adulthood, diagnosing FASD is time-consuming and costly. This study aimed to evaluate the discriminatory power of a German screening instrument for FASD in adults-the biographic screening interview (BSI-FASD). In an open-label comparative cohort study wherein a one-time survey was administered per participant, we compared 22 subjects with confirmed FASD with control groups of 15 subjects diagnosed with attention deficit hyperactivity disorder (ADHD), 20 subjects with alcohol or opiate dependence, 18 subjects with depression, and 31 controls without prenatal alcohol exposure. The BSI-FASD was found to be resource-efficient, user-friendly, comprehensible, and easily applicable. It provided an overall good convergent and discriminant validity with a sensitivity of 0.77 (adapted 0.86) and specificities between 0.70 and 1.00. The BSI-FASD subdomains differed in their power to differentiate FASD from the groups. This study established that the BSI-FASD is an efficient instrument to screen adults with suspected FASD. The BSI-FASD may facilitate future diagnostic evaluation and thereby contribute to improved treatment of affected individuals.