Purpose: The reliability of oral rehabilitation by four zygomatic implants with no anterior support remains to be determined. The aim of this systematic review was to assess the predictability of this approach in regard to implant survival, technical and biologic complications, and quality of life. Materials and Methods: An electronic literature search was conducted from September 2000 to November 2013. Human clinical trials in which oral rehabilitation was achieved by the use of four zygomatic implants with no additional placement of standard implants were included. The primary outcome was the survival rate of the zygomatic implants. In addition, random effects meta-analyses of the selected studies were applied to avoid potential bias caused by methodologic differences among studies. Results: Zygomatic implant survival rate weighted mean (WM) was 96.7% (range, 95.8% to 99.9%), with a 95% confidence interval (CI) of 92.5% to 98.5%. Only a limited number of surgical complications were reported, with orbital perforation the most significant. Similar results were obtained for prosthetic complications (few occurrences). Additionally, patient satisfaction levels were shown to be high, approaching that of the general population. Conclusion: Data from the present systematic review suggest that maxillary rehabilitation by four zygomatic implants with no anterior support is a reliable approach. Keywords: Zygomatic implant, dental implant, endosseous implant, oral rehabilitation, evidence-based dentistry