Graduated compression stockings represent a nonpharmacological approach to reduce the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) due to prolonged immobility through reducing lower limb venous stasis. A novel merino wool, double-layer, below-knee graduated compression stocking has been developed to reduce the risk of air travel-related DVT and PE. Methods: Twenty healthy adult participants were randomized to wear the novel graduated compression stocking on either the left or right leg. Doppler ultrasound measurements of popliteal venous blood flow were made on both legs over a 120-minute period. The primary outcome was peak systolic velocity in the popliteal vein at 120 minutes. Secondary outcomes included mean flow velocity, total volume flow, vein cross-sectional area, and change in ankle and calf measurements. Results: The popliteal vein peak systolic velocity was 0.35 cm/s (95% confidence intervals [CI], 0.22 to 0.49, P<0.001) higher with stocking use at 120 minutes, a difference of 24%. Mean flow velocity and total volume flow were also significantly higher with stocking use. Ankle and calf circumference were decreased with stocking use, with an overall difference of –6.3 mm (95% CI, –11.3 to –1.2, P=0.021) and –7.9 mm (95% CI, –13.3 to –2.4, P=0.011), respectively. Conclusion: The novel merino wool double-layer, below-knee graduated compression stocking increases lower limb venous blood flow during prolonged seated immobility. Its use is likely to reduce the risk of DVT and PE in situations of prolonged seated immobility, such as long-distance air travel. The reduction in lower limb swelling associated with their use suggests that the stockings are likely to have utility in the treatment of chronic venous insufficiency and lymphedema.