ABSTRACTBackgroundEvidence‐based interventions (EBI) can reduce nursing burnout and improve retention and healthcare quality. Nursing school is an ideal time to implement EBI to mitigate burnout and increase resilience in pre‐professional populations.AimThe current study tested whether Mindfulness‐Based Stress Reduction (MBSR) significantly improved stress, burnout, and wellness in a university‐based nursing school.MethodsUsing a non‐randomized clinical trial design, multilevel modeling for repeated measures tested intervention effects over time in MBSR participants (n = 73) and matched controls (n = 73), as well as potential moderation of intervention effects by modality (online vs. in‐person MBSR) and subpopulation (students vs. faculty/staff).ResultsMBSR effectively reduced perceived stress, exhaustion, and total burnout and increased positive affect and frequency of using two key mindfulness skills: observing and nonreactivity. No significant effects of the intervention were observed for disengagement from work, satisfaction with life, negative affect, or the mindfulness skills of describing, acting with awareness, and nonjudgment. Effects were similar across modality and subpopulation.Linking Evidence to ActionMBSR increases stress resilience and can be delivered effectively online and in person. Moreover, MBSR appears equally impactful for nursing students and faculty/staff. Implications for integrating EBI into schools of nursing to improve well‐being are discussed.