The ultrasonic-assisted extraction of polysaccharides (PS) from Ganoderma lucidum, was subjected to a scale-up study. 0.25 L extractor was used to optimize the extraction conditions toward maximum yield of PS. The extracted PS was observed to be reduced by increasing the scale from 1 to 6 L. To intensify the extraction, axial circulation at different stirring rates was induced and optimized in a 3 L U-tube extractor. Although circulation at 300 rpm improved the yield of PS for 3 L, introducing dispersion geometry (conical funnel) and adjusting the radiation distance in a 6 L U-tube extractor further intensified the extraction efficiency. A radiation distance of 4 cm and circulation induced using 600 rpm enhanced the PS as compared to the conventional 6 L extractor. Overall, the scale-up from 0.25 to 6 L was successful and introducing circulation and dispersion geometry intensified the extraction efficiency under similar dissipation of ultrasonic power. (c) 2015 American Institute of Chemical Engineers AIChE J, 61: 1483-1491, 2015