A factorial design at two levels and four factors was used to investigate the recovery of flavonoids from bilberry fruit by-products. Experiments were conducted in batch with aqueous ethanol as extraction solvent. Temperature (T), extraction time (E), liquid-to-solid ratio (R) and solvent composition (C) were the factors considered. The extraction yield of flavonoids, expressed as the percentage amount of extracted flavonoids to their initial amount in the plant material, was taken as the response variable. The observed response ranged between 46.3 and 80.7%. Analysis of the data showed that three out of the four main factors, namely, T, E and C, were statistically significant, their contribution increasing in the order: E < T < C. A regression model was developed by assuming a polynomial equation for the response variable including all the statistically significant variables and their interactions. The model provided an accurate description of the effect of extraction conditions on the recovery of flavonoids, both inside and outside the design space.