Age-related psychometric differences in Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) opioid use disorder (OUD) diagnostic criteria have been hypothesized, but not been tested. This study investigated DSM-5 OUD diagnostic criteria for age-related measurement noninvariance among younger adults (YAs) and middle/older adults (MOAs) with past 12-month nonmedical use of prescription opioids. People who participated in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III and reported past 12-month nonmedical use of prescription opioids were included. YAs were 18-49 years old, and MOAs were 50+ years old. Item response theory, differential item functioning (DIF), and differential test functioning were used to assess for age-related measurement noninvariance. One in 5 people met the DSM-5 OUD diagnostic criteria for OUD within the past 12 months, with the most endorsed criteria being tolerance (17.96%). DIF was identified for 3 criteria, including (1) taking opioids for longer or in larger doses than intended, (2) long periods spent obtaining/using/recovering from use, and (3) withdrawal. DIF was associated with the latent OUD severity needed to correctly endorse the criteria, with criteria being correctly endorsed at less severe levels of latent OUD for MOAs when compared with YAs. Differential test functioning analyses showed collectively the criteria had improved detection in MOAs when compared with YAs (P < 0.01). These findings suggest that there may be age-related variations in the DSM-5 OUD diagnostic criteria's ability to detect latent OUD. Future research should identify contributing factors and the influence it has on the accuracy of age-specific surveillance estimations.