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Background: Previous studies on the impact of the COVID-19 pandemic on the mental health of health-care workers have relied on self-reported screening measures to estimate the point prevalence of common mental disorders. Screening measures, which are designed to be sensitive, have low positive predictive value and often overestimate prevalence. We aimed to estimate prevalence of common mental disorders and post-traumatic stress disorder (PTSD) among health-care workers in England using diagnostic interviews., Methods: We did a two-phase, cross-sectional study comprising diagnostic interviews within a larger multisite longitudinal cohort of health-care workers (National Health Service [NHS] CHECK; n=23 462) during the COVID-19 pandemic. In the first phase, health-care workers across 18 NHS England Trusts were recruited. Baseline assessments were done using online surveys between April 24, 2020, and Jan 15, 2021. In the second phase, we selected a proportion of participants who had responded to the surveys and conducted diagnostic interviews to establish the prevalence of mental disorders. The recruitment period for the diagnostic interviews was between March 1, 2021 and Aug 27, 2021. Participants were screened with the 12-item General Health Questionnaire (GHQ-12) and assessed with the Clinical Interview Schedule-Revised (CIS-R) for common mental disorders or were screened with the 6-item Post-Traumatic Stress Disorder Checklist (PCL-6) and assessed with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) for PTSD., Findings: The screening sample contained 23 462 participants: 2079 participants were excluded due to missing values on the GHQ-12 and 11 147 participants due to missing values on the PCL-6. 243 individuals participated in diagnostic interviews for common mental disorders (CIS-R; mean age 42 years [range 21-70]; 185 [76%] women and 58 [24%] men) and 94 individuals participated in diagnostic interviews for PTSD (CAPS-5; mean age 44 years [23-62]; 79 [84%] women and 15 [16%] men). 202 (83%) of 243 individuals in the common mental disorders sample and 83 (88%) of 94 individuals in the PTSD sample were White. GHQ-12 screening caseness for common mental disorders was 52·8% (95% CI 51·7-53·8). Using CIS-R diagnostic interviews, the estimated population prevalence of generalised anxiety disorder was 14·3% (10·4-19·2), population prevalence of depression was 13·7% (10·1-18·3), and combined population prevalence of generalised anxiety disorder and depression was 21·5% (16·9-26·8). PCL-6 screening caseness for PTSD was 25·4% (24·3-26·5). Using CAPS-5 diagnostic interviews, the estimated population prevalence of PTSD was 7·9% (4·0-15·1)., Interpretation: The prevalence estimates of common mental disorders and PTSD in health-care workers were considerably lower when assessed using diagnostic interviews compared with screening tools. 21·5% of health-care workers met the threshold for diagnosable mental disorders, and thus might benefit from clinical intervention., Funding: UK Medical Research Council; UCL/Wellcome; Rosetrees Trust; NHS England and Improvement; Economic and Social Research Council; National Institute for Health and Care Research (NIHR) Biomedical Research Centre at the Maudsley and King's College London (KCL); NIHR Protection Research Unit in Emergency Preparedness and Response at KCL., Competing Interests: Declaration of interests SAMS is supported by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and an NIHR Advanced Fellowship. MH has received funding from the Innovative Medicines Initiative for the RADAR-CNS programme, a public-private pre-competitive consortium in mHealth, and his university received research funding from Janssen, Biogen, UCB, MSD, and Lundbeck. PM is supported by the NIHR Applied Research Collaboration (ARC; West) and the NIHR Biomedical Research Centre at University Hospitals Bristol, Weston NHS Foundation Trust, and the University of Bristol. NG has been an unpaid member of two NHS England expert advisory groups; and owns the company March on Stress, which is a psychological health consultancy providing mental health training to a wide range of organisations including the NHS. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)