To estimate the cost of implementing a clinical program designed to support safer use of antipsychotics in children and adolescents (youth) age 3–17 years at the time of initiating an antipsychotic medication. We calculate the costs of implementing a psychiatric consultation and navigation program for youth prescribed antipsychotic medications across 4 health systems, which included an electronic health record (EHR) decision support tool, consultation with a child and adolescent psychiatrist, and up to 6 months of behavioral health care navigation, as well as telemental health for patients (n = 348). Cost data were collected for both start-up and ongoing intervention phases and are estimated over a 1-year period. Data sources included study records and time-in-motion reports, analyzed from a health system perspective. Costs included both labor and nonlabor costs (2019 US dollars). The average total start-up and ongoing costs per health system were $34,007 and $185,174, respectively. The average total cost per patient was $2,128. The highest average ongoing labor cost components were telemental health ($901 per patient), followed by child and adolescent psychiatrist consultation ($659), and the lowest cost component was primary care/behavioral health provider time to review/respond to the EHR decision support tool and case consultation ($24). For health systems considering programs to promote safer and targeted use of antipsychotics among youth, this study provides estimates of the full start-up and ongoing costs of an EHR decision support tool, psychiatric consultation service, and psychotherapeutic services for patients and families. Trial registration: Clinicaltrials.gov, NCT03448575 [ABSTRACT FROM AUTHOR]