Purpose: To compare the 2-year survival and peri-implant bone loss of implants with and without a fluoride modification under immediate loading conditions in completely edentulous mandibles. Materials and Methods: A total of 125 Osseospeed implants (test group) were placed in 25 patients requiring a fixed rehabilitation. Implants were loaded immediately (baseline) with a provisional screw-retained prosthesis. Implant survival and bone level changes were analyzed at 3, 12, and 24 months. Results were compared with the outcome of 25 previously treated patients with immediately loaded TiOblast implants using the same treatment protocol (control group). Results: Implant survival was 100% for both groups. After 3, 12, and 24 months, the mean bone loss for the control group was 0.60, 0.81, and 0.84 mm on the patient level and 0.60, 0.80, and 0.86 mm on the implant level. For the test group, a mean bone loss of 0.14, 0.11, and 0.11 mm was for the patient; and 0.14, 0.11, and 0.11 mm with the implant as statistical unit after 3, 12, and 24 months, respectively. No statistically significant differences were observed comparing peri-implant bone loss at 3 months with 12 and 24 months in both groups, but the control group showed more peri-implant bone loss compared with the test-group (P .001). Moreover, the control group showed an increasing interquartile range over time, suggesting that not every implant is reaching steady-state bone levels. Conclusions: Immediate loading of implants placed in the completely edentulous mandible is a successful treatment option with high survival rates and limited bone loss after 2 years. However, initial crestal bone preservation significantly benefits from fluoride modification.