A combination of 5-fluorouracil and cisplatin (FP regimen) is widely used as a standard treatment for head and neck cancer. Recently, capecitabine has received increased attention. We conducted a retrospective study to compare the efficacy and safety of the FP regimen with that of the “XP regimen,” which entails concurrent chemoradiotherapy (CCRT) with capecitabine and cisplatin, in patients with resectable laryngohypopharyngeal squamous cell carcinoma (SCC). We retrospectively reviewed the records of 71 patients-67 men and 4 women, mean age 63.1 years-who had undergone CCRT from August 2004 through March 2010 as a primary treatment for resectable laryngohypopharyngeal SCC. There were 19 patients in the FP group and 52 in the XP group. With regard to chemotherapy morbidity, the XP group had less need for healthcare resources and fewer delays in treatment due to toxicity. After CCRT, a higher (but not statistically significant) rate of complete response was observed in the XP group than in the FP group (71.2 vs. 57.9%; p = 0.291); the XP group also had a better, although not significant, response among patients with neck metastases (67.7 vs. 30%; p = 0.063). During follow-up (mean: 34.8 ± 30.6 mo), recurrence rates were 25.6% in the XP group and 21.4% in the FP group-again, not a statistically significant difference (p = 0.745). At the time of the final follow-up, 20 of the 71 patients (28.2%) had died of disease. Compared with the FP group, the XP group had a significantly lower incidence of disease-specific death (21.2 vs. 47.4% respectively; p = 0.030). However, the Kaplan-Meier method identified no significant difference between the two groups in the 3-year survival rate (69.6 vs. 63.2%; p = 0.263). Overall toxicities and grade 3 or 4 toxicities (with the exception of hand-foot syndrome) were generally far less common in the XP group, with statistical significance identified for patients who experienced anemia, nausea, and vomiting. On the basis of our experience, we conclude that the results of the XP regimen were comparable to those of the FP regimen for CCRT in patients with resectable laryngohypopharyngeal SCC in terms of treatment efficacy, toxicity, and patient convenience.