A stable isotope dilution analysis (SIDA) was developed for the quantitative analysis of the health-promoting phytoalexin (E)-resveratrol in red wines by means of UPLC-QuanTOF-MS. After hemisynthetic preparation of (E)-3,5,4'-trihydroxy-2,4,6-trideuterostilbene ((E)-[(2)H(3)]-resveratrol) as the stable isotope labeled internal standard, validation experiments revealed recovery rate of 96.2 ± 0.8% RSD, thus demonstrating the robustness and accuracy of the SIDA-UPLC-QuanTOF-MS method. Repeatability and reproducibility expressed as RSD showed excellent values of 3.0% and 4.0% for (E)-[(2)H(3)]-resveratrol. Cross validation against a SIDA-HPLC-MS/MS analysis using a triple quadrupole mass spectrometer revealed comparable data, but the SIDA-UPLC-QuanTOF-MS was four times faster, thus making the latter method preferential for an accurate high-throughput analysis of wine samples. Comparison of the SIDA data to those obtained by quantitation using a standard addition method and external calibration, respectively, revealed 97.7% and 32.4% of the resveratrol concentration determined by means of SIDA-UPLC-QuanTOF-MS and 101.0% and 12.7% of the resveratrol levels found by using SIDA-HPLC-MS/MS.