Initiators play an important role in the curing of vinyl ester resins. In this study, two kinds of initiators were used to investigate the effects of initiator systems on the cure kinetics, microstructure, and mechanical properties of vinyl ester resins. The reaction kinetics, investigated with isothermal differential scanning calorimetry (DSC), showed that the combination of different kinds of initiators could significantly decrease the induction times and exothermal peak times and increase the amount of isothermal reaction heat in comparison with a single-initiator system. The residual heat of the isothermal cure of vinyl ester resins, obtained by DSC, demonstrated the existence of microheterogeneity in the cured resins. The DSC data also showed that the highly crosslinked phase (the microgel phase) was more perfect for the resins cured with an initiator-combination system. No significant difference was observed in the mechanical properties of resins cured under different conditions, whereas the cure temperature had a great effect on the mechanical properties of cured resins.