Background: Temporo-Mandibular Joint (TMJ) replacement has been used clinically for years. The objective of this study was to evaluate outcomes achieved in patients with two different categories of TMJ prostheses. Material and Methods: All patients who had a TMJ replacement (TMJR) implanted during the study period from 2006 through 2012 were included in this 3-year prospective study. All procedures were performed using the Biomet Microfixation TMJ Replacement System, and all involved replacing both the skull base component (glenoid fossa) and the mandibular condyle. Results: Fifty-seven patients (38 females and 19 males), involving 75 TMJs with severe disease requiring reconstruction (39 unilateral, 18 bilateral) were operated on consecutively, and 68 stock prostheses and 7 custom-made prostheses were implanted. The mean age at surgery was 52.6 +/- 11.5 years in the stock group and 51.8 +/- 11.7 years in the custom-made group. In the stock group, after three years of TMJR, results showed a reduction in pain intensity from 6.4 +/- 1.4 to 1.6 +/- 1.2 (p<0.001), and an improvement in jaw opening from 2.7 +/- 0.9 cm to 4.2 +/- 0.7 cm (p<0.001). In the custom-made group, after three years of TMJR, results showed a reduction in pain intensity from 6.0 +/- 1.6 to 2.2 +/- 0.4 (p<0.001), and an improvement in jaw opening from 1.5 +/- 0.5 cm to 4.3 +/- 0.6 cm (p<0.001). No statistically significant differences between two groups were detected. Conclusions: The results of this three-year prospective study support the surgical placement of TMJ prostheses (stock prosthetic, and custom-made systems), and show that the approach is efficacious and safe, reduces pain, and improves maximum mouth opening movement, with few complications. As such, TMJR represents a viable technique and a stable long-term solution for cranio-mandibular reconstruction in patients with irreversible end-stage TMJ disease. Comparing stock and custom-made groups, no statistically significant differences were detected with respect to pain intensity reduction and maximum mouth opening improvement.