Amidothionophosphates (AMTPs) are a novel group of antioxidants that are lacking in pro-oxidant activity. In this paper, we compare two different amidothionophosphates: 2-hydroxy-ethyl amido, diethyl thionophosphate (AMTP-B), which contains a single primary amido group, and N,N′,N″-tripropylamidothionophosphate (AMTP-3A), which contains three primary amido groups. The lipoprotein/medium partition coefficients of AMTP-3A and AMTP-B are 74 and 38, respectively. Both protected isolated human low density lipoprotein (LDL) against oxidative damage induced by copper sulfate. Oxidative damage to polyunsaturated acyl chains was determined by gas chromatography (GC), and oxidation kinetics were monitored by following the accumulation of conjugated dienes spectrophotometrically at 234 nm. The AMTP antioxidants significantly protected the LDL against Cu2+-Induced oxidation. However, if the LDLs were already partially oxidized, protection against oxidation by the AMTPs was reduced. AMTP-3A was more effective in protecting LDL than was AMTP-B. The difference in antioxidant activity was attributed to the 15-fold higher reactivity of AMTP-3A toward peroxides. Oxidizability of plasma lipoproteins from guinea pigs injected with AMTPs was strongly reduced.