ABSTRACT: BACKGROUND:This paper presents the protocol for the National Institute of Mental Health (NIMH)-funded University of Washington's ALACRITY (Advanced Laboratories for Accelerating the Reach and Impact of Treatments for Youth and Adults with Mental Illness) Center (UWAC), which uses human-centered design (HCD) methods to improve the implementation of evidence-based psychosocial interventions (EBPIs). We propose that usability-the degree to which interventions and implementation strategies can be used with ease, efficiency, effectiveness, and satisfaction-is a fundamental, yet poorly understood determinant of implementation. OBJECTIVE:We present a novel Discover, Design/Build, and Test (DDBT) framework to study usability as an implementation determinant. DDBT will be applied across Center projects to develop scalable and efficient implementation strategies (eg, training tools), modify existing EBPIs to enhance usability, and create usable and nonburdensome decision support tools for quality delivery of EBPIs. METHODS:Stakeholder participants will be implementation practitioners/intermediaries, mental health clinicians, and patients with mental illness in nonspecialty mental health settings in underresourced communities. Three preplanned projects and 12 pilot studies will employ the DDBT model to (1) identify usability challenges in implementing EBPIs in underresourced settings; (2) iteratively design solutions to overcome these challenges; and (3) compare the solution to the original version of the EPBI or implementation strategy on usability, quality of care, and patient-reported outcomes. The final products from the center will be a streamlined modification and redesign model that will improve the usability of EBPIs and implementation strategies (eg, tools to support EBPI education and decision making); a matrix of modification targets (ie, usability issues) that are both common and unique to EBPIs, strategies, settings, and patient populations; and a compilation of redesign strategies and the relative effectiveness of the redesigned solution compared to the original EBPI or strategy. RESULTS:The UWAC received institutional review board approval for the three separate studies in March 2018 and was funded in May 2018. CONCLUSIONS:The outcomes from this center will inform the implementation of EBPIs by identifying cross-cutting features of EBPIs and implementation strategies that influence the use and acceptability of these interventions, actively involving stakeholder clinicians and implementation practitioners in the design of the EBPI modification or implementation strategy solution and identifying the impact of HCD-informed modifications and solutions on intervention effectiveness and quality. TRIAL REGISTRATION:ClinicalTrials.gov NCT03515226 (https://clinicaltrials.gov/ct2/show/NCT03515226), NCT03514394 (https://clinicaltrials.gov/ct2/show/NCT03514394), and NCT03516513 (https://clinicaltrials.gov/ct2/show/NCT03516513). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/14990.