Purpose: The aims of this study were to assess the treatment outcome of immediately loaded full-arch screw-retained prostheses with distal extensions supported by both upright and tilted implants for the rehabilitation of edentulous jaws and to compare the outcomes of upright versus tilted implants. Materials and Methods: At 4 study centers, 342 Osseotite NT implants were consecutively placed in 65 patients (96 implants were placed in 24 mandibles and 246 implants in 41 maxillae). The 2 distal implants were tilted by 25 to 35 degrees. Provisional full-arch restorations made of a titanium framework and acrylic resin teeth were delivered within 48 hours of surgery and immediately loaded. The final prosthesis was delivered after 3 months of healing. Results: Three implants failed during the first year and another 2 within 18 months of loading in the maxilla. The cumulative implant survival rate for the maxilla was 97.59% for up to 40 months of follow-up. No implant failure was recorded for the mandible. The prosthetic success rate was 100%. Marginal bone loss around upright and tilted implants was similar. Patients were satisfied of their esthetics, phonetics, and function. Conclusion: The preliminary results of this study suggest that immediate rehabilitation of the edentulous maxilla and mandible by a hybrid prosthesis supported by 6 or 4 implants, respectively, may represent a viable treatment alternative with respect to more demanding surgical procedures. The clinical results indicate that immediately loaded tilted implants may achieve the same outcome as upright implants in both jaws. (Clinical Trial) Keywords: dental implants, edentulous jaw, immediate loading, tilted implants