Abstract This study optimised the ultrasound-assisted extraction (UAE) conditions to achieve maximal recovery of active monacolins with minimal contents of citrinin from red yeast rice (RYR). A central composite design after a full factorial design was utilised to examine the different UAE parameters. The studies revealed that HAc%, extraction time and EtOH% had significant influences on the recovery yield of monacolins, while HAc% and EtOH% were key factors for the elimination of citrinin. The resulting optimal conditions were as follows: ultrasound power of 250W, HAc% of 7.7%, RYR amount of 0.2g (solvent-to-solid ratio 40mL/g), extraction time of 50.7min, EtOH% of 57.2% and extraction temperature of 20°C. Under these conditions, at least 94.7% of monacolins was recovered and 87.7% of citrinin was removed from RYR. This optimised UAE condition was further evaluated for potential industrial application in manufacturing of RYR as pharmaceuticals and nutraceuticals.