The present work evaluated antibody-coated liposomes as a new treatment strategy for immune thrombocytopenic purpura (ITP) through the use of a mouse model of the disease. Effects of antimethotrexate antibody (AMI)–coated liposomes and intravenous immunoglobulin (IVIG)–coated liposomes (15, 30, 60 μmol lipid/kg) were compared with the effects of IVIG (0.4, 1, 2 g/kg) and anti–red blood cell (anti-RBC) monoclonal antibody immunotherapy (TER119, 5, 15, 25, and 50 μg/mouse) on MWReg30-induced thrombocytopenia. Each treatment was found to attenuate thrombocytopenia in a dose-dependent manner and, consistent with previous work, IVIG was found to increase antiplatelet antibody clearance in a dose-dependent manner. TER119 demonstrated greater effects on thrombocytopenia relative to other therapies (peak platelet counts: 224% ± 34% of initial platelet counts for 50 μg TER119/mouse versus 160% ± 34% for 2 g/kg IVIG, 88% ± 36% for 60 μmol lipid/kg AMI-coated liposomes, and 80% ± 25% for 60 μmol lipid/kg IVIG-coated liposomes). However, the effects of TER119 were associated with severe hemolysis, as TER119 decreased RBC counts by approximately 50%. The present work demonstrated that antibody-coated liposomes attenuated thrombocytopenia in this model at a much lower immunoglobulin dose than that required for IVIG effects and, in contrast with TER119, antibody-coated liposomes increased platelet counts without altering RBC counts.