PURPOSE The US Preventive Services Task Force recommends screening for depression in the general adult population. Although screening questionnaires for depression and anxiety exist in primary care settings, electronic health tools such as computerized adaptive tests based on item response theory can advance screening practices. This study evaluated the validity of the Computerized Adaptive Test for Mental Health (CAT-MH) for screening for major depressive disorder (MDD) and assessing MDD and anxiety severity among adult primary care patients. METHODS We approached 402 English-speaking adults for participation from a primary care clinic, of whom 271 adults (71% female, 65% black) participated. Participants completed modules from the CAT-MH (Computerized Adaptive Diagnostic Test for MDD, CAT-Depression Inventory, CAT-Anxiety Inventory); brief paper questionnaires (9-item Patient Health Questionnaire [PHQ-9], 2-item Patient Health Questionnaire [PHQ-2], Generalized Anxiety Disorder 7-item Scale [GAD-7]); and a reference-standard interview, the Structured Clinical Interview for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) Diagnoses. RESULTS On the basis of the interview, 31 participants met criteria for MDD and 29 met criteria for GAD. The diagnostic accuracy of the Computerized Adaptive Diagnostic Test for MDD (area under curve [AUC] = 0.85) was similar to that of the PHQ-9 (AUC = 0.84) and higher than that of the PHQ-2 (AUC = 0.76) for MDD screening. Using the interview as the reference standard, the accuracy of the CAT-Anxiety Inventory (AUC = 0.93) was similar to that of the GAD-7 (AUC = 0.97) for assessing anxiety severity. The patient-preferred screening method was assessment via tablet/computer with audio. CONCLUSIONS Computerized adaptive testing could be a valid and efficient patient-centered screening strategy for depression and anxiety screening in primary care settings.