Sit-stand stools are available for use in industrial settings, but there is a lack of quantitative evidence demonstrating benefits for lower limb, back and/or neck/shoulder outcomes. In this paper we describe an experiment conducted to compare and contrast posture and time-related differences in muscular and vascular outcomes during 34 min of manual repetitive work performed in either standing or sit-standing work posture. We measured vascular parameters in the lower limbs, and muscular parameters in the trunk and neck/shoulder, and discomfort in the three regions as participants accomplished a repetitive box-folding task. Results show that blood flow in the foot (p = 0.022) and ankle mean arterial pressure (p < 0.001) were greater during standing. Left gluteus medius and external oblique activation was higher during standing, while sit-standing work resulted in higher levels of co-activation between the left erector spinae and external oblique muscle pair (p = 0.026). Neck/shoulder muscle activity was not significantly different between the conditions. Reported discomfort did not differ significantly for the trunk and neck/shoulder region, but standing resulted in higher level of reported discomfort in the lower limb. The sit-stand posture used in this experiment appears to prevent the undesirable lower limb outcomes associated with static standing work posture.This work demonstrates quantitative evidence to support the potential use of a sit-stand stool for industrial work operations, at least over relatively short durations.