Peanut skins are a rich source of oligomeric and polymeric procyanidins. The oligomeric fractions are dominated by dimers, trimers, and tetramers. A multistep chromatographic fractionation led to the isolation of four new A-type procyanidins of tri- and tetrameric structures. The structures of the new trimers were defined by NMR, electronic circular dichroism, and MS data as epicatechin-(4β→8,2β→O→7)-epicatechin-(4β→8,2β→O→7)-catechin, peanut procyanidin B (3), and epicatechin-(4β→8,2β→O→7)-epicatechin-(4β→6)-catechin, peanut procyanidin C (4). The new tetramers were defined as epicatechin-(4β→8,2β→O→7)-epicatechin-(4β→6)-epicatechin-(4β→8,2β→O→7)-catechin, peanut procyanidin E (1), and epicatechin-(4β→8,2β→O→7)-epicatechin-(4β→6)-epicatechin-(4β→8,2β→O→7)-epicatechin, peanut procyanidin F (2). In addition, both A-type dimers A1, epicatechin-(4β→8,2β→O→7)-catechin, and A2, epicatechin-(4β→8,2β→O→7)-epicatechin, as well as two known peanut trimers, ent-epicatechin-(4β→6)-epicatechin-(4β→8,2β→O→7)-catechin, peanut procyanidin A (5), and epicatechin-(4β→8)-epicatechin-(4β→8,2β→O→7)-catechin, peanut procyanidin D (6), were also isolated. Dimer A1, the four trimers, and two tetramers were evaluated for anti-inflammatory activity in an in vitro assay, in which LPS-stimulated macrophages were responding with secretion of TNF-α, a pro-inflammatory cytokine. Tetramer F (2) was the most potent, suppressing TNF-α secretion to 82% at 8.7 μM (10 μg/mL), while tetramer E (1) at the same concentrations caused a 4% suppression. The results of the TNF-α secretion inhibition indicate that small structural differences, as in peanut procyanidin tetramers E and F, can be strongly differentiated in biological systems.