Purpose: The aim of this retrospective follow-up study was to determine whether implant-supported reconstructions on customized computer-milled abutments will loosen less frequently than those placed on prefabricated abutments. Materials and Methods: Suprastructures on prefabricated abutments (n = 312) were compared with those on customized computer-milled abutments (n = 96) over an observation period of 2 years. In all cases, the suprastructures had been cemented on the abutments with zinc oxide-eugenol cement (ZEC). Both groups were subdivided into single-crown restorations, fixed dental prostheses (FDPs) with two implants, and FDPs with more than two implants. The data were evaluated on the denture level. Results: Of the restorations on prefabricated abutments, 8% loosened, and of those on customized abutments, 3.1% loosened. The difference was not significant. Of the single crowns on prefabricated abutments, 7.7% loosened, and of those on customized abutments, 0% loosened. The difference was significant. For the FDPs with two implants (prefabricated abutments: 9.7%; customized abutments: 10.7%; not significant) and the FDPs with more than two implants (prefabricated abutments: 0%; customized abutments: 11.1%; significance not analyzed), statistical evaluation was difficult because of the small number of cases. Conclusions: Loosening of reconstructions placed on customized abutments can be reduced for single-crown restorations. When ZEC is used, customized abutments offer a valid alternative to prefabricated abutments. The small number of cases of FDPs with two implants and FDPs with more than two implants made statistical evaluation impossible.