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To aid intracellular delivery, drug carrier nanoparticles have been used to overcome the barrier imposed by the plasma membrane. The carrier must entrap large amounts of cargo, efficiently and quickly deliver the cargo in the cytosol or other intracellular compartments, and must be inert; they should not induce cellular responses or alter the cell state in the course of delivery. This study demonstrates that cationic liposomes with high charge density efficiently fuse with synthetic membranes and the plasma membrane of living cells. Direct fusion efficiently delivers large amounts of cargo to cells and cell\u2010like vesicles within seconds, bypassing slow and often inefficient internalization\u2010based pathways. These effects depend on liposome charge density, concentration, and the helper lipid. 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