Aim The World Health Organization Disability Assessment Schedule II (WHODAS II) was developed for assessing disability. This study provides data on the validity and utility of the Spanish version of the WHODAS II in a large sample of patients with schizophrenia. Methods The sample included 352 patients with a schizophrenia spectrum disorder. They completed a comprehensive assessment battery including measures of psychopathology, functionality and quality-of-life. A sub-sample of 36 patients was retested after six months to assess its temporal stability. Results Participation in society (6.3%) and Life activities (4.0%) were the domains with the highest percentage of missing data. The internal consistency (Cronbach's alpha) of the total scale was 0.94, and the test–retest stability reached an intraclass correlation coefficient of 0.92. It became apparent that the six primary factor models represent a better fit with reality than other competing models. Relationships between the WHODAS and measures of symptomatology, social and work-related functionality, and quality-of-life were in the expected direction and the scale was ultimately found to be able to differentiate among patients with different degrees of disease severity and different work status. Conclusions Assessment of disability using appropriate tools is a crucial aspect in the context of mental health and, in this regard, the Spanish version of the WHODAS II shows ample evidence of validity in patients with schizophrenia. The most important contribution of this study is that it is the first analyzing the Spanish version of the WHODAS II (36-item version) in a large sample of patients with schizophrenia.