Purpose: To evaluate the outcome of three (fixed-on-3 = Fo3) vs four (fixed-on-4 = Fo4) implants immediately restored with metal-resin screw-retained cross-arch prostheses in fully edentulous jaws. Materials and methods: Forty-eight edentulous or to be rendered edentulous patients were randomised in six centres (eight patients per centre) to the Fo3 group (24 patients: 12 maxillae and 12 mandibles) and to the Fo4 group (24 patients: 12 maxillae and 12 mandibles) according to a parallel group design. To be immediately loaded, implants had to be inserted with a minimum torque of 40 Ncm. Outcome measures were prosthesis and implant failures, complications and peri-implant marginal bone level changes evaluated up to 1 year post-loading. Results: One maxillary prosthesis per group was delayed loaded because implants could not be placed with a torque of at least 40 Ncm. Ten patients in the Fo3 group and four in the Fo4 group had implants placed flapless. One year after loading no drop out occurred. One patient of the Fo3 group lost three implants vs three patients of the Fo4 group who lost four implants, the difference being no statistically significant (risk difference = -0.08; 95% CI: -0.27 to 0.10; Fisher's exact test P = 0.609). One mandibular Fo3 and one maxillary Fo4 prosthesis failed. Six Fo3 patients were affected by complications vs three Fo4 patients (risk difference = 0.12; 95% CI: -0.10 to 0.34; Fisher's exact test; P = 0.461). Both groups lost marginal bone in a statistically significant way (0.22 ± 0.20 mm for Fo3 patients and 0.40 ± 0.21 mm for Fo4 patients), with Fo3 group showing less marginal peri-implant bone loss than Fo4 group (estimate of the difference = -0.18 (standard error: 0.06) mm; 95% CI: -0.30 to -0.06; P = 0.005). There were no differences in clinical outcomes between the six operators. Conclusions: These preliminary results suggest that immediately loaded cross-arch prostheses of both jaws can be supported by only three dental implants at least up to 1 year post-loading, though longer follow-ups are definitively needed.