Objective To explore the optimal strategy for fiber-reinforced composite (FRC) post-and-resin core restoration on an endodontically-treated maxillary first molar with a disto-occluso-palatal ( DOP ) defect. Methods Eight different finite element models of FRC post-resin core restored maxillary first molar were established. In the multi-post groups, the thinner post was horizontally trimmed 1 mm below the intersection point as the adjunct post, and the thicker one was resignated as the main post. The 800 N vertical force parallel to the long axis of the tooth and 225 N lateral force directed at 45° to the long axis of the tooth were applied. The equivalent stresses on external surfaces of tooth tissues, internal surfaces of root canals and in the posts, as well as the maximum shear stresses on post-cement interfaces and cement-dentin interfaces were calculated with finite element analysis. Results All the models showed similar distribution patterns of equivalent stress on external surfaces of tooth tissues under the same loading. The maximum equivalent stress was found on palatal (P) side of the root trunk under vertical loading, and on mesiobuccal ( MB) side of root trunk under lateral loading. On internal surfaces of root canals, the maximum equivalent stress increased at the middle third of post- placed canal, and decreased at the cervical third of the canal. Under vertical loading, P posts showed the highest equivalent stress, while MB posts showed the highest equivalent stress under lateral loading. Under vertical loading, the main post encountered larger shear stress than the assistant one on post-cement interface in the same canal. Under lateral loading, post-cement interface in MB canal showed the highest shear stress. The highest shear stress appeared on cement-canal interface with a P post under vertical loading, and with an MB post under lateral loading. Conclusions The FRC post restoration can transmit occlusal force towards apical area, so as to improve stress distributions in residual tooth tissues for a maxillary first molar with DOP defect. One post in the P canal may be the best strategy of FRC post and resin core restoration for an endodontically- treated maxillary first molar with a DOP defect.