There is a great interest in searching for new environmentally sustainable techniques to enhance the use of agricultural byproducts. In this work, a response surface methodology was used to study the influence of the two independent variables, temperature (25-200 °C) and extraction time (3-17 min), in the extraction of antioxidants by pressurized hot water extraction (PHWE) from industrial apple byproducts. The optimized extraction method for determination of flavonols was at 120 °C and 3 min, giving a predicted total yield of flavonols of 1.3 μmol/g dry apple byproduct. Results obtained suggest that new antioxidant compounds were formed at the higher extraction temperatures. A desirability function response surface, considering maximum antioxidant capacity and minimal formation of brown color, was calculated and gave an optimum of 125 °C and 3 min. This latter PHWE method correlates well with the obtained results for flavonols; thus, a desirability function is a simpler alternative method for finding optimal conditions.