Objectives/Hypothesis High rates of overall survival (OS) and laryngeal preservation were achieved in two sequential phase II clinical trials in patients with stage III/IV laryngeal squamous cell carcinoma (SCC). Patients were treated with chemoradiation after a >50% primary tumor response to one cycle of neoadjuvant chemotherapy (IC). We analyzed outcomes for T4 patients with cartilage invasion from both studies. Study Design: Retrospective. Methods: Records from 36 patients with T4 SCC of the larynx with cartilage invasion alone (n = 16) or cartilage invasion and extralaryngeal spread (n = 20) were retrospectively reviewed. All were treated with one cycle of cisplatin (100 mg/m 2) [or carboplatin (AUC 6)] and 5-fluorouracil (1,000 mg/m 2/d for 5 days) (P+ 5FU). Those achieving >50% response at the primary tumor received chemoradiation (70 Gy; 35 fractions with concurrent cisplatin-100 mg/m 2 [car- boplatin (AUC 6)] every 21 days for 3 cycles), followed by adjuvant P+5FU for complete histologic respond- ers (CHR). Patients with <50% response after IC underwent total laryngectomy and postoperative radiation. Results: Twenty-nine of 36 patients (81%) had >50% response following IC. Of these, 27 received definitive chemoradiation, 23 (85%) obtained CHR, with 58% laryngeal preservation rate. The 3-year OS was 78%, and the disease-specific survival was 80% (median follow-up 69 months). Following chemoradiation, 8/11 (73%) patients with an intact larynx had > 75% understandable speech, 6/36 (17%) were g- tube dependent and 6/36 (17%) were tracheostomy dependent. Conclusions: Our results suggest that chemo- selection is a feasible organ preservation alternative to total laryngectomy for patients with T4 laryngeal SCC with cartilage invasion.