Highly stressed employees are subject to greater health risks, increased cost, and productivity losses than those with normal stress levels. To address this issue in an evidence-based manner, worksite stress management programs must be able to engage individuals as well as capture data on stress, health indices, work productivity, and health care costs. In this randomized controlled pilot, our primary objective was to evaluate the viability and proof of concept for two mind-body workplace stress reduction programs (one therapeutic yoga-based and the other mindfulness-based), in order to set the stage for larger cost-effectiveness trials. A second objective was to evaluate 2 delivery venues of the mindfulness-based intervention (online vs. in-person). Intention-to-treat principles and 2 (pre and post) × 3 (group) repeated-measures analysis of covariance procedures examined group differences over time on perceived stress and secondary measures to clarify which variables to include in future studies: sleep quality, mood, pain levels, work productivity, mindfulness, blood pressure, breathing rate, and heart rate variability (a measure of autonomic balance). Two hundred and thirty-nine employee volunteers were randomized into a therapeutic yoga worksite stress reduction program, 1 of 2 mindfulness-based programs, or a control group that participated only in assessment. Compared with the control group, the mind-body interventions showed significantly greater improvements on perceived stress, sleep quality, and the heart rhythm coherence ratio of heart rate variability. The two delivery venues for the mindfulness program produced basically equivalent results. Both the mindfulness-based and therapeutic yoga programs may provide viable and effective interventions to target high stress levels, sleep quality, and autonomic balance in employees.