Introduction Office employees are exposed to hazardous levels of sedentary work. Interventions that integrate health promotion and health protection elements are needed to advance the health of sedentary workers. This study tested an integrated intervention on occupational sedentary/physical activity behaviors, cardiometabolic disease biomarkers, musculoskeletal discomfort, and work productivity. Design Two-group, RCT. Data were collected between January and August 2014. Setting/participants Overweight/obese adults working in sedentary desk jobs were randomized to: (1) a health protection–only group (HPO, n =27); or (2) an integrated health protection/health promotion group (HP/HP, n =27). Intervention HPO participants received an ergonomic workstation optimization intervention and three e-mails/week promoting rest breaks and posture variation. HP/HP participants received the HPO intervention plus access to a seated activity permissive workstation. Main outcome measures Occupational sedentary and physical activity behaviors (primary outcomes), cardiometabolic health outcomes, musculoskeletal discomfort, and work productivity (secondary outcomes) were measured at baseline and post-intervention (16 weeks). Results The HP/HP group increased occupational light intensity physical activity over the HPO group and used the activity permissive workstations 50 minutes/work day. Significant associations were observed between activity permissive workstation adherence and improvements in several cardiometabolic biomarkers (weight, total fat mass, resting heart rate, body fat percentage) and work productivity outcomes (concentration at work, days missed because of health problems). Conclusions The HP/HP group increased occupational physical activity and greater activity permissive workstation adherence was associated with improved health and work productivity outcomes. These findings are important for employers interested in advancing the well-being of sedentary office workers. Trial registration This study is registered at www.clinicaltrials.gov NCT02071420.