BACKGROUND: Prolonged sitting time is a health risk. We describe a practice-based study designed to reduce prolonged sitting time and improve selected health factors among workers with sedentary jobs. COMMUNITY CONTEXT: We conducted our study during March-May 2011 in Minneapolis, Minnesota, among employees with sedentary jobs. METHODS: Project implementation occurred over 7 weeks with a baseline period of 1 week (period 1), an intervention period of 4 weeks (period 2), and a postintervention period of 2 weeks (period 3). The intervention group (n = 24) received a sit-stand device during period 2 designed to fit their workstation, and the comparison group (n = 10) did not. We used experience-sampling methods to monitor sitting behavior at work during the 7 weeks of the project. We estimated change scores in sitting time, health risk factors, mood states, and several office behaviors on the basis of survey responses. OUTCOME: The Take-a-Stand Project reduced time spent sitting by 224% (66 minutes per day), reduced upper back and neck pain by 54%, and improved mood states. Furthermore, the removal of the device largely negated all observed improvements within 2 weeks. INTERPRETATION: Our findings suggest that using a sit-stand device at work can reduce sitting time and generate other health benefits for workers.