To assess the clinical efficacy of posterior composite resin restorations placed directly and indirectly in posterior teeth after five years. A total of 108 cavities in 54 patients were restored with three direct composite resins (Filtek SupremeXT [FSXT], Tetric Evo Ceram [TEC], AELITE Aesthetic [AA]) and two indirect composite resins (Estenia [E] and Tescera ATL [TATL]). All restorations were evaluated by two examiners using the United States Public Health Service criteria at baseline and five years after placement. Statistical analysis was completed with Fisher exact and McNemar χ(2) tests. At baseline, 4% (five) of the restored teeth presented postoperative sensitivity; however, only one of them (a member of the E group) required canal treatment and replacement after two years. At the five-year evaluation, all restorations were retained, with Alpha ratings at 100%. Only one tooth (in the TEC group) required replacement after three years due to secondary caries. Color match, surface texture, and marginal integrity were predominantly scored as Alpha after five years for all groups. After that time, marginal discoloration was scored as Alpha in 64% of AE restorations, 70% of TATL restorations, 73% of E restorations, and 87% of FSXT restorations. There were no Charlie scores recorded for any of the restorative systems. Under controlled clinical conditions, indirect composite resin inlays and direct composite resin restorations exhibited an annual failure rate of 2.5% and 1.6%, respectively, after five years. Therefore, the investigated materials showed acceptable clinical performance, and no significant differences were found among them.