Purpose: The purpose of this retrospective study was to evaluate the 5-year clinical performance and failure rate of single- or multiple-unit zirconia-based crowns. Materials and Methods: A total of 148 patients (39 men and 109 women, mean age: 46.9 ± 10.6 years) treated in university and private practices with 618 single- or multiple-unit zirconia-based (Lava) crowns made on natural teeth from January 2007 to December 2008 were included. Two hundred fifty-nine anterior and 359 posterior crowns were examined. A core and/or veneer fracture that required replacement of the restoration was considered to be a failure. The cumulative survival rate (CSR) was described with Kaplan-Meier survival functions. The crowns replaced for other reasons were deemed lost to follow-up, and esthetic, functional, and biologic complications were rated. Results: At the 5-year follow-up, no zirconia core fractures were observed. Twelve veneer fractures that required crown replacement were detected. The CSR was 98.1%. There was a statistically significant difference between survival of the anterior and posterior restorations (P .001). In total, 116 crowns experienced biologic and technical complications. The most common complications were smooth veneer fracture (4, 0.6%), loss of retention (7, 1%), staining because of smoking (24, 4%), and gingival recession (48, 8%). Conclusions: According to the 5-year CSR (98.1%) observed in this study, zirconia-based single or multiple crowns may be considered an acceptable treatment modality for the replacement of anterior and posterior teeth. Results from the current study should be supported by additional randomized clinical trials.