Background: Concurrent chemoradiation therapy (CCRT) with every 3 week schedule of cisplatin is the standard treatment for locally advanced nasopharyngeal carcinoma (NPC), but concerns have been raised about treatment-related complications. We conducted a randomized phase II non-inferiority study of CCRT with three week versus weekly cisplatin to compare the efficacy and toxicity profiles. Methods: From September 2009 through August 2011, 111 patients with locally advanced NPC who have stage II-IVb were enrolled from 22 centers in Korea. Patients were randomized into treatment groups that either received cisplatin 100 mg/m² every 3 weeks for 3 cycles (arm A) or cisplatin 40 mg/m² weekly for 7 cycles (arm B) concurrently with RT. Subsequent adjuvant chemotherapy, cisplatin 80 mg/m² day 1 and fluorouracil 1,000 mg/m²/day day 1-4 was administered every 3 weeks for a total of 3 cycles. Results: Of the 109 eligible patients, 56 were assigned to arm A, and 53 to arm B. The two arms were well-balanced in all prognostic factors and RT parameters. There was no significant difference in RT dose (67.28 Gy vs 68.30 Gy, p=0.559) or cisplatin dose (257 vs 249 mg/m², p=0.433) between two arms. About 90% of patients in both arms completed protocols of CCRT. However, 29% of patients in arm A and 45% of those in arm B received subsequent adjuvant chemotherapy (p=0.045). Overall tumor response was 97 % but no difference was noted in tumor response between two arms (96 vs 98%, p=1.000). Overall, the grade 3/4 toxicities were similar between the two arms. The most common grade 3/4 adverse events during CCRT were neutropenia (15% in arm A vs 28% in arm B), stomatitis (13% vs 15%), and nausea/vomiting (11% vs 8%). Conclusions: These results demonstrated that weekly regimen of cisplatin as CCRT is well tolerated and shows similar treatment efficacy compared with 3 weekly schedule of cisplatin in patients with locally advanced NPC. Longer follow-up is needed to evaluate the final results of progression free survival and overall survival.