Difficulties in performing activities of daily living (ADL) are common in patients with Korsakoff‘s syndrome (KS). The aim of this study was to identify factors associated with ADL dependence in nursing home residents with KS. This exploratory, cross-sectional study included 281 residents with KS from 9 specialized nursing homes in the Netherlands. We examined demographic, cognitive, somatic, and (neuro)psychiatric characteristics. ADL dependence was assessed with the Inter-RAI ADL Hierarchy Scale. Multivariable logistic regression analyses were used to identify factors associated with ADL dependence. Cognitive impairment (odds ratio [OR] = 7.46; 95% confidence interval [CI] = 2.10–30.5), female gender (OR = 3.23; CI, 1.21–8.78), staying in a nursing home for ≥5 years (OR = 3.12; CI, 1.24–8.33), and impaired awareness (OR = 4.25; CI, 1.56–12.32) were significantly associated with higher ADL dependence. Chronic obstructive pulmonary disease (COPD) was significantly associated with lower ADL dependence (OR = 0.31; CI, 0.01–0.84). The model explained 32% of the variance. The results suggest that when choosing interventions aimed at improving ADL functioning, special attention should be paid to residents living more than five years in the nursing home, with a female gender, with more severe cognitive impairments, and/or with COPD.