In order to optimize ultrasonic-assisted extraction of flavonoids from water caltrop pericarp, response surface methodology was used to acquire regression models for optimization of extraction temperature, extraction time and ethanol concentration based on single factor investigations. The results showed that this model reflected good relationship of the flavonoids yield and these factors. The optimal conditions for achieving the high extraction yield of flavonoids were temperature of 71.77 ℃, time of 37.96 min and ethanol concentration of 51.82%. Under the optimum conditions, the extraction yield of flavonoids reached 5.61% and fitted the models well. The obtained model could be used for extraction of total flavonoids from water caltrop pericarp.