Solvent composition has a large influence on measured antioxidant potential (AOP) of model polyphenols and red wines with 2,2-diphenyl-1-picrylhydrazyl (DPPH). We have shown that incorporation of aqueous buffer in the assay medium results in higher reactivity of catechin and caftaric acid, which are among major polyphenolic constituents of wines. Consequently, AOPs of red wines determined after 60 min of incubation at 25 °C in buffered methanol are 1.5-1.6-fold of values determined in methanol. Even in buffered methanol, wine polyphenols are not fully oxidized after 60 min. Only about half of Trolox equivalents were determined in comparison to the Folin-Ciocalteu assay. Buffer composition, pH, time of incubation, temperature, and concentration of antioxidants and DPPH all contribute to the resulting value of the AOP being standardized or at least strictly reported because minor differences in experimental procedures can account for large variations in determined AOP with DPPH for the same samples.