Objectives Given the complex demands of many workplaces, there is growing interest in the potential beneficial effects of mindfulness-based programs (MBPs) for employees. This meta-analysis systematically synthesizes the results of randomized controlled studies conducted in various workplace settings. Methods Eligible studies were identified by a systematic literature search in four electronic databases and complementary manual search strategies through 11/2018. Random-effects models were used to synthesize data across 56 studies including n  = 2689 participants and n  = 2472 controls. The validity of synthesized effect size estimates was analyzed for heterogeneity and influential cases (outliers). Risk of bias was assessed following Cochrane recommendations. Results Analyses of between-group effects indicated that MBPs effectively reduce stress, burnout, mental distress, and somatic complaints, while improving mindfulness, well-being, compassion, and job satisfaction—all with small to large effect sizes ranging from Hedge’s g  = 0.32 to 0.77. Results were maintained in follow-up assessments ≤ 12 weeks. Heterogeneity among primary studies was not explained consistently by program or participant characteristics in the exploratory moderator analyses. Results on work engagement and productivity were limited by low numbers of primary studies with outliers among their effect sizes. Conclusions Our meta-analysis provides evidence that MBPs effectively promote the health and well-being of employees in various occupational settings. Further research is needed to investigate potential benefits on work-related outcomes and effects for longer-term follow-ups.