Purpose: The aim of this prospective study was to evaluate the clinical efficacy and long-term survival rate of three-unit fixed partial dentures (FPDs) made from lithium disilicate-based core ceramic. Materials and Methods: Twenty-one threeunit FPDs were placed in 19 patients to replace single lost teeth in the esthetic area, following a study protocol that took clinical, esthetic, and radiologic aspects into consideration. Each case was reviewed at 1 week following placement, at 6 months, and then annually for 10 years. Statistical analysis was performed using Kaplan- Meier survival analysis. Results: Out of the 19 patients, 14.3% presented reversible postoperative sensitivity. Recession was observed in 24% of dental posts, and 7.1% presented marginal discoloration. Treatment did not increase either Bleeding or Plaque Index scores at prepared teeth; secondary caries did not appear either. The restorations' survival rate at the 10-year follow-up was 71.4%; six FPDs had fractured and one debonded. Conclusions: Fracture failure rate was 28.6% after 10 years; a high percentage corresponded to connector fractures and occurred during the first 5 years. Lithium disilicate glass-ceramic FPDs present a higher risk of fracture than standard therapies (metal-ceramic) or other more recently developed ceramic materials. The prognosis for survival improves for Class I occlusion and nonparafunctional patients.