The Deglutition Handicap Index (DHI) is a self-report measure for patients at risk of oropharyngeal dysphagia on deglutition-related aspects of functional health status (FHS) and health-related quality of life (HR-QoL). The DHI consists of 30 items which are subsumed within the Symptom, Functional and Emotional subscales. The purpose of this study was to evaluate the psychometric properties of the DHI using Classic Test Theory according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. A total of 453 patients with dysphagia with different aetiologies were recruited concurrently at two academic hospitals. Dysphagia was confirmed by fiberoptic endoscopic and/or videofluoroscopic evaluation of swallowing. In addition, a healthy control group of 132 participants were recruited. Structural validity was determined using exploratory and confirmatory factor analyses and internal consistency by calculating Cronbach’s alpha coefficients. Hypothesis testing was evaluated using Mann–Whitney U-tests, linear regression analysis and correlations analysis. Diagnostic performance and receiver operating characteristic curves analysis were calculated. Factor analyses indicated that the DHI is a unidimensional measure. The DHI has good internal consistency with some indication of item redundancy, weak to moderate structural validity and strong hypothesis testing for construct validity. The DHI shows high diagnostic performance as part of criterion validity. These findings support that the DHI is an appropriate choice as a patient self-report measure to evaluate FHS and HR-QoL in dysphagia. Ongoing validation to assess the measure for possible item redundancy and to examine the dimensionality of the DHI using item response theory is recommended.