Background Mindfulness-based stress reduction (MBSR), which was initially used in clinical settings, has also proved to be an effective tool for managing work-related stress in occupational groups inherently exposed to certain psychosocial risks. Aims To examine the potential for work-related stress management using MBSR for middle-level managers who are considered to be particularly affected by the negative effects of stress related to organizational restructuring. Methods Middle-level managers participated in a randomized controlled study which implemented a 2 (experimental versus control group) x 2 (baseline, post-treatment) study design, yielding a between-group comparison. The participants were randomly assigned to an 8-week intervention group or to a wait-list control group. Results The results showed that, relative to the control group, the MBSR intervention had significant effects on several outcomes in the 144 subjects, including: decreases in perceived work-related stress (F(1,140) = 20.4, P < 0.001, d(diff) = 0.72), negative affect (F(1,140) = 45.3, P < 0.001, d(diff) = 0.93), intensity of somatic complaints (F(1,140) = 20.7, P < 0.001, d(diff) = 0.69), and sickness absence (F(1,140) = 67.3, P < 0.001, d(diff) = 0.69), and increase in self-esteem (F(1,140) = 44.1, P < 0.001, d(diff) = 1.25), and positive affect (F(1,140) = 6.73, P < 0.01, d(diff) = 0.43). No effects were found on frequency of somatic complaints. Conclusions These results suggest that MBSR is an effective method for managing work-related stress and bolstering psychological resilience in the workplace, particularly in the face of psychosocial risks of a global, economic nature.