Purpose: To evaluate the clinical outcome of two implants placed flapless in fully edentulous mandibles and immediately restored with metal-resin screw-retained cross-arch prostheses 5 years after loading. Materials and methods: Eighty consecutive patients were recruited. To be immediately loaded, implants had to be inserted with a minimum torque of 80 Ncm. Forty-six laser-welded titanium and 34 cast silver-palladium frameworks with resin teeth were initially delivered within 8 and 48 h, respectively. Outcome measures, evaluated by two independent assessors included prosthesis and implant failures, complications, marginal bone level changes, implant stability quotient (ISQ) values and patient satisfaction. Results: Five years after loading one patient did not return to the control and 10 prostheses were remade. Two implants failed early in two patients, but they were successfully replaced. Thirty-six complications occurred in 28 patients but were all successfully treated. After 5 years, mean marginal bone loss was 0.69 mm, mean ISQ values decreased from 75.4 to 73.8, and all patients were fully satisfied with the therapy. A post-hoc comparison between the outcome of laser-welded and cast frameworks showed that laser-welded frameworks were affected by significantly more complications (19 patients out of 46 and 6 patients out of 34, respectively; difference in proportion = 0.23, 95% CI: 0.03 to 0.43; Pearson's chi-square test, P = 0.032), therefore such a framework construction should be considered as a long-term temporary prosthesis and not a definitive prosthesis. Conclusions: Immediately loaded mandibular cross-arch prostheses can be supported by only two implants up to 5 years, if made with a robust cast framework. Longer follow-ups (around 10 years) are still needed to know the prognosis of this treatment modality. Keywords: cohort study, dental implants, flapless, immediate loading