Background: It is unknown which regimen is the best in concurrent chemoradiotherapy (CCRT) of locally advanced non-squamous non-small cell lung cancer (NSCLC). Our previous randomized phase Ⅱ study, NJLCG0601, showed that chemoradiotherapy with uracil/tegafur (UFT) and cisplatin achieved promising efficacy with acceptable toxicities. In this trial, this regimen was compared to a regimen with pemetrexed and cisplatin for stage Ⅲ non-squamous NSCLC. Methods: Patients with inoperable stage Ⅲ non-squamous NSCLC were randomized to UFT 400 mg/m² on days 1–14 and 29–42, and cisplatin 80 mg/m² on days 8 and 36 (UP), or pemetrexed 500 mg/m² and cisplatin 75 mg/m² on days 1, 22, and 43 (PP). Involved-field radiotherapy (IFRT) was administered from day 1 to a total dose of 66 Gy radiotherapy in 33 fractions. Consolidation chemotherapy after CCRT was not planned for this study. The primary endpoint was 2-year overall survival (OS), with expected rates of 55% and a lower limit of 35% (alfa 0.05, beta 0.2). Secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), OS, and toxicity profile. Results: From November 2010 to June 2017, 86 patients were enrolled from 11 institutions. Of the 85 eligible patients, the rate of 2-year OS was 78.6% (95% CI: 62.8–88.3%) in the UP arm and 85.5% (95% CI: 70.5–93.2%) in the PP arm. The ORR was 76.7% in the UP arm and 81.0% in the PP arm. With a median follow-up of 54 months, median PFS and OS were 12.3 and 64.2 months in the UP arm, and 26.2 months and not reached in the PP arm, respectively. Grade 3/4 febrile neutropenia was more frequent in the UP arm than in the PP arm (14.0%, 2.0%, respectively). Grade 3/4 pneumonitis occurred in 7.0% and 4.8% of patients in UP and PP arms, respectively. Conclusions: Both regimens with IFRT achieved the expected 2-year survival rate. PP had more favorable results than UP in terms of OS and PFS. We selected the PP arm for the next step.