The effect of the peroxide initiator nature on the grafting of itaconic acid (IA) onto low-density polyethylene (LDPE) was investigated in the course of the reactive extrusion. It was shown that at other equal conditions, the solubility of the peroxide initiator in the molten polymer is most important in the IA grafting onto LDPE. The thermal stability of peroxide initiators is also important, At the synthesis conditions of preparing the grafted products by the reactive extrusion, peroxides, which decompose at temperatures far below the IA melting point (also in the feed zone of the extruder), can be used to initiate grafting reactions. It is very probable that radicals formed from peroxide decomposition interact first with LDPE macromolecules, while the formed macroradicals initiate IA grafting reactions. Peroxides, which are easily dissolved in LDPE, are recommended for initiating the efficient grafting reactions. The closer the thermodynamic affinity between the peroxide and the monomer, the less the efficiency of grafting. Higher transportation velocities of the reactive blend in the extruder-reactor intensify LDPE crosslinking, thus lowering the IA grafting efficiency.