Anticholinergic burden defined by the Anticholinergic Risk Scale (ARS) has been associated with cognitive and functional decline. Associations with health-related quality of life (HRQoL) have been scarcely studied. The aim of this study was to examine the association between anticholinergic burden and HRQoL among older people living in long-term care. Further, we investigated whether there is an interaction between ARS score and HRQoL in certain underlying conditions.