The aim of this research was to optimize the extraction condition of ultrasound-assisted extraction (UAE) of phenols from the red grape of Vranac variety (Vitis vinifera L.) pomace seeds. The minimum experiments needed for optimization of UAE by response surface methodology (RSM) were obtained by spectrophotometric and HPLC analyses of seed extracts. UAE greatly depends on three independent variables: extraction temperature, time and liquid/solid ratio. The RSM can be used for optimization of UAE conditions to obtain maximum responses such as extraction yield, TPC, (+)-catechin, (-)-epicatechin and proanthocyanidin content. The predicted values of the model were in accordance with experimental data under the same conditions (RSD was 0.74%). Experimental data also confirmed that UAE gives a better yield of phenolics than conventional solvent extraction (23.76% increase). The UAE under optimal extraction conditions is suitable for obtaining extracts that are rich in phenolic content, and have strong antioxidant activity which could be used as additives in food and medicaments.