Objectives <p>This trial assessed the feasibility, effectiveness, and sustainability of a mindfulness-based intervention (MBI) for reducing stress in healthcare professionals in acute inpatient care. Research questions addressed the MBI’s feasibility and impact on mindfulness, burnout-related discomfort, overall quality of life, and team atmosphere.</p> Method <p>Twenty female hospital employees from oncology, obstetrics, or surgery departments in a Swiss tertiary hospital participated. A prospective within-subject pre-post design was used for this feasibility trial. Participants underwent a modified version of Kabat-Zinn’s Mindfulness-Based Stress Reduction (MBSR) program, including sessions and daily self-guided practice. Mindfulness, burnout-related discomfort, overall quality of life, and team atmosphere were assessed using validated instruments. A qualitative focus group interview evaluated the program.</p> Results <p>Mindful Attention Awareness Scale (MAAS) scores increased non-significantly. Burnout Screening Scale (BOSS) scores significantly decreased in burnout-related discomfort, especially in “Physical discomforts” (<i>p</i> &lt; 0.002; Kendall’s <i>W</i> = 0.31). WHO Quality of Life-BREF (WHOQOL-BREF) scores for “health-related overall quality of life” significantly improved (<i>p</i> &lt; 0.02; Kendall’s <i>W</i> = 0.19). Positive changes in team atmosphere were observed. Focus group interviews emphasized the importance of mindfulness and potential for team communication improvement, recommending its implementation for the entire team.</p> Conclusions <p>The MBI showed feasibility and potential effectiveness in reducing burnout-related discomfort and improving overall quality of life among healthcare professionals in acute inpatient settings. Joint mindfulness practice also enhanced team atmosphere. Further controlled studies are needed to confirm these findings.</p> Preregistration <p>This study is not preregistered.</p>