In 2017, the National Academy of Medicine convened its Action Collaborative for Clinician Well-being and Resilience in an effort to stem the epidemic levels of burnout, depression, and suicide among healthcare clinicians. Nurses report higher rates of substance abuse, depression, and suicide than the national average. Newly licensed registered nurses (NLRNs) report high levels of burnout and stress. Suboptimal health in nurses is linked to medical errors. Few studies address the mental health and lifestyle behaviors of NLRNs or provide evidence-based solutions to improve these outcomes.This study evaluated the 6-month effects of the MINDBODYSTRONG for Healthcare Professionals program on the mental health, healthy lifestyle behaviors, and job satisfaction of NLRNs participating in a nurse residency program.A two-group randomized controlled trial was conducted with 89 NLRNs at a large, Midwestern academic medical center. The intervention group received eight 30- to 35-min weekly sessions as part of the MINDBODYSTRONG program, a cognitive behavioral skill-building program incorporating strategies to improve mental and physical health. The control group acted as the attention control group receiving eight weekly 30- to 35-min debriefing sessions as part of the normal nurse residency program.Data were collected at baseline, immediately postintervention, 3 months postintervention, and 6 months postintervention. The intervention group scored better on mental health outcomes, healthy lifestyle behaviors, and job satisfaction at 6 months postintervention than the control group. Significant improvements were found for depressive symptoms and job satisfaction; there were moderate to large positive effects for the MINDBODYSTRONG program on all variables.The MINDBODYSTRONG program sustained its positive effects across time and has excellent potential as an evidence-based intervention for improving the mental health, healthy lifestyle behaviors, and job satisfaction in NLRNs.