OBJECTIVES: Healthcare workers, most notably nursing professionals, face high levels of recurrent stress that lead to symptoms of burnout and other negative mental health outcomes. This indicates the need for greater individual and organizational health system support, including implementation of effective, evidence-based interventions for burnout reduction in this population. Organizationally supported mindfulness-based interventions can be used to build individual resilience, buffering the detrimental effects of occupational stress and enhance professional well-being. Our aim was to evaluate the effect of an evidence-based mindfulness intervention on perceived stress, burnout, resilience, and work engagement in nursing professionals. METHODS: A non-randomized single arm, pre/post design was used for this study. Healthcare workers (n = 631), including Registered Nurses and Advanced Practice Nurses (n = 128), physicians (n = 105), social workers (n = 21), pharmacists (n = 8), chaplains (n = 30), physician and occupational therapists (n = 39), patient care assistants (n = 13), other clinical staff (n = 26), non-clinical staff (n = 229), and 32 others participated in Mindfulness in Motion, an 8-week evidence-based worksite mindfulness intervention. Validated self-report measures assessing burnout (Maslach Burnout Inventory), perceived stress (Perceived Stress Scale), resilience (Connor Davidson Resiliency Scale), and work engagement (Utrecht Work Engagement Score) were given pre and post program. Total burnout was determined by scores on the subscales of emotional exhaustion, depersonalization, and personal accomplishment of the Maslach Burnout Inventory: Emotional exhaustion >27 or depersonalization >13 or personal accomplishment <31. RESULTS: Significant reductions in burnout (p < 0.00001), perceived stress (p < 0.00001), with significant increases in resilience (p < 0.00001), and work engagement (p < 0.00001) were observed among Registered and Advanced Practice Nurses comparing pre-post measures. Notably, the number of nursing professionals who no longer qualified as burned out was 10% higher than the other participants. CONCLUSION: Our results suggest that nursing professionals could greatly benefit from organizationally supported mindfulness-based interventions such as Mindfulness in Motion and may benefit them most compared to other health system employees.