Objective: To explore the application effect of different materials in the restoration of inlay crown for patients with large-area dental defects after root canal therapy. Methods: A total of 107 patients with large-area dental defects after root canal therapy were enrolled. According to different restoration materials, they were divided into zirconia group (36 cases, 41 teeth), cast porcelain group (35 cases, 40 teeth) and resin group (36 cases, 43 teeth). All were followed up for 24 months to evaluate the restoration effect, functional recovery, exhibition of aesthetics, periodontal health and complications. Results: At 18 and 24 months after restoration, success rate of restoration, bite force, masticatory efficiency and periodontal health indexes in zirconia group were better than those in cast porcelain group and resin group (P<0.05). The comprehensive scores of color matching and aesthetics in cast porcelain group were higher than those in zirconia group and resin group(P<0.05). There was no significant difference in morphological coordination or surface smoothness between zirconia group and cast porcelain group (P>0.05), but which in the two groups were better than those in resin group(P<0.05). There were statistically significant differences in the incidence of complications among the three groups of patients(P<0.05), the incidence of complications was the lowest in zirconia group, while which was the highest in resin group(P<0.05). Conclusion: Zirconia has the best long-term restoration effect, functional recovery and safety, cast porcelain has significant aesthetic advantages, and resin is suitable for short-term transitional restoration. In clinical practice, selection should be made according to one’s needs.