BACKGROUND/AIMS: Mindfulness-based stress reduction (MBSR) has enhanced cognition, positive emotion, and immunity in younger and middle-aged samples; its benefits are less well known for older persons. Here we report on a randomized controlled trial of MBSR for older adults and its effects on executive function, left frontal asymmetry of the EEG alpha band, and antibody response. METHODS: Older adults (n = 201) were randomized to MBSR or waiting list control. The outcome measures were: the Trail Making Test part B/A (Trails B/A) ratio, a measure of executive function; changes in left frontal alpha asymmetry, an indicator of positive emotions or approach motivation; depression, mindfulness, and perceived stress scores, and the immunoglobulin G response to a protein antigen, a measure of adaptive immunity. RESULTS: MBSR participants had a lower Trails B/A ratio immediately after intervention (p < 0.05); reduced shift to rightward frontal alpha activation after intervention (p = 0.03); higher baseline antibody levels after intervention (p < 0.01), but lower antibody responses 24 weeks after antigen challenge (p < 0.04), and improved mindfulness after intervention (p = 0.023) and at 21 weeks of follow-up (p = 0.006). CONCLUSIONS: MBSR produced small but significant changes in executive function, mindfulness, and sustained left frontal alpha asymmetry. The antibody findings at follow-up were unexpected. Further study of the effects of MBSR on immune function should assess changes in antibody responses in comparison to T-cell-mediated effector functions, which decline as a function of age.