Objectives: To compare toxic effects and functional outcomes of reirradiation with and without salvage surgery for nonnasopharyngeal mucosal head and neck squamous cell carcinoma. Design: Retrospective review. Setting: Academic tertiary referral hospital. Patients: Between December 1992 and March 2007, a total of 87 patients underwent reirradiation (64 for cure and 23 for palliation). Intervention: Patients underwent reirradiation with (n = 38) or without salvage surgery (n = 49). After January 2000 there was increased use of concurrent platinumbased chemotherapy (80% vs 5%) and intensitymodulated radiation therapy (82% vs 0%). Main Outcome Measures: Early and late toxic effects of treatment by Radiation Therapy Oncology Group criteria, tracheostomy retention, gastrostomy tube dependence, and survival. Results: The median follow-up among patients alive at last contact was 5.0 years. Compared with reirradiation without surgery, postoperative reirradiation was associated with increased early grade 3 to grade 5 toxic effects (50% [19 of 38] vs 29% [14 of 49], P = .04) and with longer median survival (17.3 vs 8.9 months, P < .001). Freeflap reconstruction decreased early toxic effects in the surgical cohort by 16% (from 60% [9 of 15] to 43% [10 of 23], P = .32). Gastrostomy tube dependence (P = .05) and tracheostomy retention (P = .04) have increased since 2000. The median survival for curative patients was 12.5 months. The estimated 2-year survival was 25%, and the estimated 5-year survival was 8%. Conclusions: Reirradiation represents the only chance for cure in patients with unresectable disease. After surgery, reirradiation is performed in patients at high risk of locoregional recurrence and may increase acute toxic effects. However, free-flap reconstruction may reduce toxic effects. Functional outcomes have declined since 2000 likely because of the addition of concurrent platinum-based chemotherapy. Future research may define the subpopulation of postoperative patients for whom survival benefits most outweigh reirradiation toxic effects. ©2009 American Medical Association. All rights reserved.