Liver dysfunction often is associated with an imbalance in the production and removal of free radicals derived from oxygen and nitrogen and has been managed clinically with antioxidant supplements, including silymarin extract derived from milk thistle. The potential for enhanced bioavailability of a phytosome complex containing phosphatidylcholine and silybin, the primary active flavonolignan in silymarin extract, was tested in dogs. A group of eight beagles (four males, four females) were dosed orally with a silybin–phosphatidylcholine complex (SPC) and a commercially available standardized silymarin extract containing equivalent levels of silybin. Dosing with the SPC resulted in Cmax, Tmax, and AUC0−24h values (mean ± SD) for total silybin of 1310 ± 880 ng/mL, 2.87 ± 2.23 h, and 11 200 ± 6520 ng·h/mL, respectively; corresponding values for a standardized silymarin extract were 472 ± 383 ng/mL, 4.75 ± 2.82 h, and 3720 ± 4970 ng·h/mL. A second, separate group of beagles were also dosed with the extract alone, yielding values of 449 ± 402 ng/mL, 6.87 ± 7.43 h, and 2520 ± 2976 ng·h/mL. These data show that a phytosome complex of phosphatidylcholine and silybin markedly enhances bioavailability in dogs.