Although mindfulness-based stress reduction (MBSR) can improve health and well-being, less is known about factors that predict outcomes. This prospective observational study examined gender and baseline anxiety and sleep quality as predictors of change in emotion regulation and stress symptoms following an 8-week MBSR program. Women and men reported similar improvement in stress symptoms and cognitive reappraisal, whereas men improved more in emotion suppression. Individuals with higher anxiety and worse sleep pre-treatment benefited most in terms of decreased stress. Evaluating pre-treatment characteristics could help determine optimal candidates for MBSR training, and could optimize outcomes for both women and men.