Purpose: The purpose of this retrospective study was to compare the functional outcomes of patients who had mandibular resection and reconstruction with and without prosthetic intervention, and to identify predictive factors that may have an impact on functional outcomes. Materials and Methods: Two hundred twenty head and neck cancer patients who had undergone mandibular resection and reconstruction with at least 6 months of postoperative convalescence formed the basis of this retrospective review. Patients who did not receive prosthetic intervention formed group I (n = 142); those who received prosthetic intervention formed group II (n = 78). Functional outcomes were measured using four individual assessments (nutritional status, swallowing, masticatory performance, and speech) and one that combined the information from these assessments, the global measure of functional outcome (GMFO). Statistical analyses were used to compare the baseline characteristics and functional outcome between groups I and II and to analyze independent predictors for GMFO. Results: Of the 220 patients reviewed, 78 (35%) had prosthetic intervention; group II patients had better individual functional outcome measures and GMFO. Use of a prosthesis remained associated with GMFO after controlling for other significant predictors; other independent predictors were xerostomia, number of remaining mandibular teeth, number of tooth-to-tooth contacts, type of reconstruction, flap interference, and tongue defect. Patients who had fewer mandibular teeth and received a smaller prosthesis had better overall outcome than patients who received a larger prosthesis. Conclusion: Patients who had prosthetic intervention after mandibular reconstruction had significantly better functional outcomes than patients who did not receive prosthetic intervention, even after adjusting for confounding variables.