Purpose: To assess the clinical performance of lithium disilicate single restorations on natural teeth. Materials and Methods: All patients who received lithium disilicate single restorations between 2009 and 2013 at the dental clinic of the University of Ferrara were recalled for clinical evaluation. A total of 43 partial and total restorations in 17 patients were evaluated from a minimum of 36 months follow-up to a maximum of 81 months follow-up, with a mean follow-up of 51 months. Results: The cumulative survival rate was 97.7%, and the cumulative success rate was 94.2%. Conclusion: Lithium disilicate can be successfully used for single-tooth restorations.