Aim: To compare the clinical, radiographic, and prosthetic outcomes of zirconia-polyether ether ketone (PEEK) versus acrylic resin-metal mandibular full-arch fixed detachable implant prostheses (FDIP) during a two-year follow-up. Materials and methods: Twelve completely edentulous participants were selected. For each patient, six implants were installed in the mandible using a flapless surgical technique. Participants were randomly assigned to one of two groups: zirconia-PEEK FDIP or acrylic-metal FDIP. The clinical and radiographic parameters were assessed at prosthesis insertion, then after one and two years. The prosthetic complications were recorded from the time of prosthesis insertion for two years. Results: There were statistically significant differences in plaque and gingival indices as well as probing depth between the two groups, where the acrylic-metal group showed higher clinical outcome values than the zirconia-PEEK group. The zirconia-PEEK group showed significantly higher crestal bone loss than the acrylic-metal group. During the whole follow-up period, there were (n = 36, 62% of the total complications) prosthetic complications in the acrylic-metal group and (n = 22, 38 % of the total complications) in the zirconia-PEEK group. The total number of prosthetic complications was not significantly greater in the acrylic-metal group than in the zirconia-PEEK groups. There were no fractures of the prosthetic framework or abutment in either group. Conclusion: Within the limits of this study, zirconia-PEEK full-arch FDIP produces better clinical and prosthetic outcomes than acrylic-metal FDIP. However, zirconia-PEEK FDIP may lead to higher crestal bone loss than acrylic-metal FDIP.