Objectives: To assess 1-year incidence and factors related to deprescribing in nursing home (NH) residents in Europe. Design: Longitudinal multicenter cohort study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study. Setting: NHs in Europe and Israel. Participants: 1843 NH residents on polypharmacy. Methods: Polypharmacy was defined as the concurrent use of 5 or more medications. Deprescribing was defined as a reduction in the number of medications used over the study period. Residents were followed for 12 months. Results: Residents in the study sample were using a mean number of 8.6 (standard deviation 2.9) medications at the baseline assessment. Deprescribing was observed in 658 residents (35.7%). Cognitive impairment (mild/moderate impairment vs intact, odds ratio [OR] 1.41, 95% confidence interval [CI] 1.11-1.79; severe impairment vs intact, OR 1.60, 95% CI 1.23-2.09), presence of the geriatrician within the facility staff (OR 1.41, 95% CI 1.15-1.72), and number of medications used at baseline (OR 1.10, 95% CI 1.06-1.14) were associated with higher probabilities of deprescribing. In contrast, female gender (OR 0.76, 95% CI 0.61-0.96), heart failure (OR 0.69, 95% CI 0.53-0.89), and cancer (OR 0.64, 95% CI 0.45-0.90) were associated with a lower probability of deprescribing. Conclusions and Implications: Deprescribing is common in NH residents on polypharmacy, and it is associated with individual and organizational factors. More evidence is needed on deprescribing, and clear strategies on how to withdraw medications should be defined in the future.