Despite limited efficacy and significant safety concerns, antipsychotic medications are frequently used to treat behavioral and psychological symptoms of dementia (BPSD) in long-term residential care. This study evaluates the sustained reduction of antipsychotic use for BPSD through a deprescribing intervention and education of health care professionals.Repeated-measures, longitudinal, single-arm study.Long-term residential care of older adults.Nursing staff from 23 nursing homes recruited 139 residents taking regular antipsychotic medication for ≥3 months, without primary psychotic illness, such as schizophrenia or bipolar disorder, or severe BPSD.An antipsychotic deprescribing protocol was established. Education of general practitioners, pharmacists, and residential care nurses focused on nonpharmacological prevention and management of BPSD.The primary outcome was antipsychotic use over 12-month follow-up; secondary outcomes were BPSD (Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory, and social withdrawal) and adverse outcomes (falls, hospitalizations, and cognitive decline).The number of older adults on regular antipsychotics over 12 months reduced by 81.7% (95% confidence interval: 72.4-89.0). Withdrawal was not accompanied by drug substitution or a significant increase in pro-re-nata antipsychotic or benzodiazepine administration. There was no change in BPSD or in adverse outcomes.In a selected sample of older adults living in long-term residential care, sustained reduction in regular antipsychotic use is feasible without an increase of BPSD.