Violations of rules and regulations in research can cause significant problems for human participants, animal subjects, data integrity, institutions, and investigators. The Professionalism and Integrity in Research Program (PI Program) provides remediation training that addresses the root causes of violations of rules and regulations in research. Through assessments, a three-day workshop, and follow-up coaching calls, the PI Program teaches evidence-based decision-making strategies designed to help researchers to compensate for bias, uncertainty, and work-related stress, and foster the skills needed to oversee research projects in today’s complex regulatory environments. Across its first three years (2013–2015), the program trained 39 researchers from 24 different institutions in the United States. Participant evaluations of the program’s faculty and workshop content were highly positive (4.7–4.8 and 4.5–4.6, respectively, on a 5-point scale). Preliminary program outcome assessment using validated measures of professional decision making and cognitive distortions in a pre- and postworkshop design indicated significant improvements. A follow-up survey of participants found statistically significant increases in a variety of target behaviors, including training research staff members to foster compliance and research quality, using standard operating procedures to support compliance and research integrity, performing self-audits of research operations, reducing job stressors, actively overseeing the work of the research team, and seeking help when experiencing uncertainty. Assessment of the PI Program was conducted with modest sample sizes, yet evaluation, outcome assessment, and self-reported survey data provided statistically significant evidence of effectiveness in achieving program goals.