Purpose: To assess the clinical performance of a two-piece zirconia implant system, with a focus on biologic complications. Materials and Methods: A total of 39 patients received 91 two-piece zirconia implants. The patients were recruited from two private clinics and were monitored for 5 to 12 years (median: 5.6 years). The primary outcomes were biologic complications, such as peri-implant infections (peri-implant mucositis and peri-implantitis), and the secondary outcome was radiographically evident marginal bone loss (MBL). Results: Three patients (7.7%) with 9 total implants (9.9%) presented with peri-implant mucositis. MBL that did not exceed the first thread was evident at 32 mesial sites (35%) and 25 distal sites (27.4%). MBL exceeding the first thread but not the third thread was evident at 6 mesial and 5 distal sites (thread pitch: 0.7 mm). Only one peri-implant pocket deepened (4 mm) and showed bleeding; however, the estimated MBL did not exceed 1.65 mm. No peri-implantitis occurred, and no implant was lost. Conclusions: This prospective study shows high survival rates and a seemingly low prevalence of biologic and prosthetic complications for this two-piece zirconia implant system over an observation period of up to 12 years.