BACKGROUND: Sedentary time is associated with chronic disease and premature mortality. We tested a multilevel workplace intervention with and without sit-stand workstations to reduce sedentary time and lower cardiometabolic risk. METHODS: Stand and Move at Work was a group (cluster) randomized trial conducted between January 2016 and December 2017 among full-time employees; ≥18 years; and in academic, industry/healthcare, and government worksites in Phoenix, Arizona and Minneapolis/St. Paul, Minnesota, USA. Eligible worksites were randomized to (a) MOVE+, a multilevel intervention targeting reduction in sedentary time and increases in light physical activity (LPA); or (b) STAND+, the MOVE+ intervention along with sit-stand workstations to allow employees to sit or stand while working. The primary endpoints were objectively-measured workplace sitting and LPA at 12 months. The secondary endpoint was a clustered cardiometabolic risk score (blood pressure, glucose, insulin, triglycerides, and HDL-cholesterol) at 12 months. RESULTS: Worksites (N = 24; academic [n = 8], industry/healthcare [n = 8], and government [n = 8] sectors) and employees (N = 630; 27 ± 8 per worksite; 45 ± 11 years of age, 74% female) were enrolled. All worksites were retained and 487 participants completed the intervention and provided data for the primary endpoint. The adjusted between arm difference in sitting at 12 months was - 59.2 (CI: - 74.6,-43.8) min per 8 h workday, favoring STAND+, and in LPA at 12 months was + 2.2 (- 0.9,5.4) min per 8 h workday. Change in the clustered metabolic risk score was small and not statistically significant, but favored STAND+. In an exploratory subgroup of 95 participants with prediabetes or diabetes, the effect sizes were larger and clinically meaningful, all favoring STAND+, including blood glucose, triglycerides, systolic blood pressure, glycated hemoglobin, LDL-cholesterol, body weight, and body fat. CONCLUSIONS: Multilevel workplace interventions that include the use of sit-stand workstations are effective for large reductions in sitting time over 12 months. Among those with prediabetes or diabetes, clinical improvements in cardiometabolic risk factors and body weight may be realized. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02566317 . Registered 2 October 2015, first participant enrolled 11 January 2016.