The main objective of this paper is to test the psychometric properties of the World Health Organization’s instrument (WHOQOL-DIS) in assessing the quality of life (QoL) in a sample of persons with disabilities in Malaysia. The sample consisted of 300 respondents who were stratified based on types of disabilities (hearing and speech, visual and physical impairment). Classical and modern psychometric methods were used to assess the reliability and validity while Cronbach’s alpha (α) and Item-total correlation matrix to test the instrument scales and subscales for reliability. Construct validity of the WHOQOL-DIS instrument was assessed using both convergent and discriminant validity. Validity DISQOL module was evaluated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The WHOQOL-DIS was found to have acceptable levels of reliability and validity for persons with disabilities within the sample. Cronbach’s alpha ranged from 0.60 to 0.83 across domains with alpha scores greater than or equal to 0.6 considered acceptable and of adequate internal consistency. Convergent and discriminant validity were satisfactory. Significant correlation was found between each item and the domain to which it had been assigned. The instrument was able to discriminate between healthy and unhealthy respondents for all domains. EFA and CFA revealed similar models of DISQOL module on par with the original version. The results provide satisfactory evidence of the validity and reliability of the WHOQOL-DIS as an instrument in assessing the QoL of Persons with Disabilities in Malaysia.