This column describes a series of interventions to decrease antipsychotic polypharmacy in the New York State Office of Mental Health (NYSOMH) network of psychiatric hospitals. Phase 1 consisted of implementation of the Psychiatric Services Clinical Knowledge Enhancement System (PSYCKES), a Web-based application supporting clinical decision making and quality improvement, and a policy requiring approval by NYSOMH’s medical director to prescribe more than two antipsychotics per patient. In phase 2 hospital leaders received feedback from the office of the medical director identifying specific patients on polypharmacy. In phase 3, access to PSYCKES continued, but the prior-approval policy and feedback were discontinued. Polypharmacy decreased significantly during phase 1, from 16.9 to 9.7 inpatients per 1,000, and decreased further in phase 2, to 3.9 inpatients per 1,000. In phase 3 the prevalence of antipsychotic polypharmacy remained low at six-month follow-up (3.1 inpatients per 1,000), despite the ending of state-level oversight. On long-term follow-up, polypharmacy increased, eventually rising to 9.2 inpatients per 1,000 after 36 months, but remained well below baseline levels. (Psychiatric Services 62:1124–1126, 2011)