Purpose: This study compared the surgical protocol efficacy of immediate and delayed implant loading in edentulous maxillae opposed by natural or restored mandibular dentitions over an observational period of 6 years or longer. The selected outcome determinants included individual implant survival data, progressive measurements of peri-implant bone resorption, prosthodontic survival and success data, and report of complications. Materials and Methods: A convenience sample of 49 patients requiring fixed implant-supported maxillary prostheses was split into two groups. The test group (34 patients) was treated according to the Columbus Bridge Protocol, which prescribes the insertion of four to six implants, including distally tilted implants, and load within 24 hours. The control group (15 patients) was treated via a two-stage surgical protocol of 6 to 9 straight implants that were loaded a mean 8.75 months after stage-one implant surgery. Two hundred sixty implants (test: n = 163, control: n = 97) were placed, and all subjects were ultimately treated with screw-retained full-arch prostheses. Results: Two patients dropped out (one in the test group and one in the control group) by the time of the scheduled sixth annual visit. The other patients were followed up for 75.2 months (range: 72 to 90 months). At the 6-year follow-up, no differences in implant cumulative survival rates were found between groups. Significantly less bone loss was found in the test group (mean: 1.62 mm) compared with the control group (mean: 2.44 mm). All of the original prostheses were maintained throughout the study's observation period and were functioning satisfactorily at each patient's last recall appointment. Conclusion: Patients who received immediate and delayed implant loading in their edentulous maxillae demonstrated similar survival outcomes. However, less marginal bone loss was recorded around the immediately loaded implants over the study's 6-year follow-up period.