Abstract Compassionate and effective pain management after surgery represents a foundation of humane medical care. Opioids still present the mainstay of post-surgical pain therapy: more than 80% of patients are prescribed opioids for use following surgery. During one year in the U.S., more than 17% of Americans fill at least one opioid prescription, and, per prescription, the average daily amount exceeded 45 milligram morphine equivalents. In addition to common side effects, serious risks of opioids include addiction, abuse, and overdose. Prescription overdose deaths contribute to more than one-third of all opioid overdose deaths and remain five-fold higher than in 1999. Over-prescription of opioids remains extremely common, with up to 90% of patients after common surgical procedures reporting leftover opioids. Unused opioids are stored in unsecured locations in 75% of cases and can create a reservoir that fuels the ongoing opioid epidemic. Most large-scale efforts, such as the CDC guidelines for prescribing opioids, have focused on chronic opioid use. There is an urgent need to increase access to high-quality, safe, and scalable interventions to reduce our reliance on opioids for effective post- surgical pain management at discharge. A diverse team with expertise in pain medicine, perioperative outcomes, clinical trials, biostatistics, and health economics has been assembled to conduct the Efficiency And Quality In Post-Surgical Pain Therapy After Discharge “EQUIPPED” study. Our central hypothesis is that pain therapy after surgery can and should be prescribed in a safer, patient-centered fashion, as opposed to current “one-size-fits- all” methods. To test this hypothesis, three aims are proposed: Specific Aim 1 will test a provider-facing EHR- based decision support tool that suggests outpatient opioid prescriptions based on inpatient opioid requirements. This aim will utilize a pragmatic randomized cluster multiple crossover controlled trial design in about 39,000 patients in four hospitals. Specific Aim 2 will test a patient-facing health informatics app that encourages non- opioid pain management strategies. This aim employs a randomized controlled trial design in 600 surgical patients. Two separate clinical trials are proposed because of different outcomes (amount of opioids prescribed vs. opioids used) and scopes of implementation (multisite vs. single site). The provider-facing tool will be incorporated into the trial of the patient-facing app using a 2x2 design that facilitates a detailed evaluation of the individual effects of these interventions, as well as any interactions when using the interventions together. Finally, Specific Aim 3 will include a cost-effectiveness analysis and compare the individual and combined cost- effectiveness of a provider-facing and a patient-facing intervention. Completion of this project will demonstrate that the amounts of opioids prescribed and opioids taken after discharge following surgery can be redu...