Few studies have been found that to assess the factors that explain higher levels of family burden in adults with intellectual disability (ID) and intellectual disability and mental disorders (ID-MD). The aims of this study were to assess family burden in people with ID and ID-MD and to determine which sociodemographic, clinical and functional disability variables account for family burden. The sample is composed of pairs of 203 participants with disability and their caregivers, of which 33.5% are caregivers of people with ID and 66.5% of ID-MD. Assessments were performed using scales of clinical and functional disability as the following instruments: Weschler Adult Intelligence Scale-III (WAIS-III), Inventory for Client and Agency Planning (ICAP), Psychiatric Assessment Schedule for Adults with Development Disability (PAS-ADD checklist), Disability Assessment Schedule of the World Health Organization (WHO-DAS-II) and family burden (Subjective and Objective Family Burden Inventory - SOFBI/ECFOS-II). People with ID-MD presented higher levels of functional disability than those with ID only. Higher levels of family burden were related to higher functional disability in all the areas (p<0.006-0.001), lower intelligence quotient (p<0.001), diagnosis of ID-MD (p<0.001) and presence of organic, affective, psychotic and behavioral disorders (p<0.001). Stepwise multiple regression showed that behavioral problems, affective and psychotic disorder, disability in participation in society, disability in personal care and presence of ID-MD explained more than 61% of the variance in family burden. An integrated approach using effective multidimensional interventions is essential for both people with ID and ID-MD and their caregivers in order to reduce family burden.