The Mental Health Inventory (MHI-5) is frequently used as a screener for mood and anxiety disorders. However, few population-based studies have validated it against a diagnostic instrument assessing disorders following current diagnostic criteria. Within the third Netherlands Mental Health Survey and Incidence Study (NEMESIS-3), a representative population-based study of adults (N=6194; age: 18-75years), the MHI-5 was used to measure general mental ill-health in the past month. Presence of mood (major depressive disorder, persistent depressive disorder, or bipolar disorder) and anxiety disorders (panic disorder, agoraphobia, social phobia, or generalized anxiety disorder) in the past month was assessed with a slightly modified version of the Composite International Diagnostic Interview 3.0 per the Diagnostic and Statistical Manual of Mental disorders-5. The MHI-5 was good to excellent at distinguishing people with and without a mood disorder, an anxiety disorder, and any mood or anxiety disorder. The cut-off value associated with the highest sensitivity and highest specificity for mood disorder was ≤68, and ≤76 for an anxiety disorder or any mood or anxiety disorder. The MHI-5 can identify individuals at high risk of a current mood or anxiety disorder in the general population when diagnostic interviews are too time consuming.