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Objective: Describe and validate the CHROME (CHemical Restraints avOidance MEthodology) criteria., Design: Observational prospective longitudinal study., Setting: Single nursing home in Las Palmas de Gran Canaria, Spain., Participants: 288 residents; mean age: 81.6 (SD 10.6). 77.4% had dementia., Intervention: Multicomponent training and consultancy program to eliminate physical and chemical restraints and promote overall quality care. Clinicians were trained in stringent diagnostic criteria of neuropsychiatric syndromes and adequate psychotropic prescription., Measurements: Psychotropic prescription (primary study target), neuropsychiatric syndromes, physical restraints, falls, and emergency room visits were semi-annually collected from December 2015 to December 2017. Results are presented for all residents and for those who had dementia and participated in the five study waves (completer analysis, n=107)., Results: For the study completers, atypical neuroleptic prescription dropped from 42.7% to 18.7%, long half-life benzodiazepines dropped from 25.2% to 6.5%, and hypnotic medications from 47.7% to 12.1% (p<0.0005). Any kind of fall evolved from 67.3 to 32.7 (number of falls by 100 residents per year). Physicians' diagnostic confidence increased, while the frequency of diagnoses of neuropsychiatric syndromes decreased (p<0.0005)., Conclusions: Implementing the CHROME criteria reduced the prescription of the most dangerous medications in institutionalized people with dementia. Two independent audits found no physical or chemical restraint and confirmed prescription quality of psychotropic drugs. Adequate diagnosis and independent audits appear to be the keys to help and motivate professionals to optimize and reduce the use of psychotropic medication. The CHROME criteria unify, in a single compendium, neuropsychiatric diagnostic criteria, prescription guidelines, independent audit methodology, and minimum legal standards. These criteria can be easily adapted to other countries.