To evaluate, over a 2-year period, the treatment outcomes for maxillary full-arch fixed dental prostheses (FDPs) supported by a combination of both tilted and axially-placed implants and to compare the marginal bone loss (MBL) and implant survival rates (SR) between tilted and axial implants. A retrospective study has been carried out. Thirty-two patients (16 males and 16 females) treated with maxillary full-arch FDPs were included in this retrospective study. A total of 187 implants were inserted to rehabilitate the fully edentulous maxillary arches: 36% of them were tilted (T group, n = 68) and the remaining 64% were axially placed (A group, n = 119). From the total, 28% of the implants (n=53) were immediately loaded with screw-retained provisional acrylic restorations, whereas 72% underwent conventional delayed prosthetic loading 6 months post-operatively. Definitive restorations were hybrid implant prostheses (metal framework covered with high-density acrylic resin) and metal-ceramic screw-retained implant prostheses, and were placed 6 months after surgery. Such definitive restorations were checked for proper function and aesthetics every three months for two years. Peri-implant marginal bone levels were assessed by digital radiographs immediately after surgery and MBL was assessed at definitive implant loading (baseline) and 2 years afterwards. The 2-year implant SR were 100% for axially placed implants and 98.5% for tilted implants. No significant differences were found amongst the A and T implant groups. Marginal bone loss measured at 2 years after definitive prosthetic loading was of -0.73 ± 0.72 mm (maximum MBL of 1.43 mm) for axially positioned implants vs. ?0.51 ± 0.92 mm for tilted implants (maximum bone 1.45 mm). Differences in MBL were statistically significant when comparing immediately and delayed loaded implants. Based on the results of this retrospective clinical study, full-arch fixed prostheses supported by a combination of both tilted and axially placed implants may be considered a predictable and viable treatment modality for the prosthetic rehabilitation of the completely edentulous maxilla.