Background: CapeOX is widely used as a six month adjuvant chemotherapy regimen of colorectal cancer which does not need central vein catheter insertion. However, oxaliplatin-related vascular pain interferes with peripheral administration. We assessed the prophylactic effect of COX-2 inhibitors on oxaliplatin-related vascular pain. Methods: A multicenter of Yokohama Clinical Oncology Group in Japan, open label, randomized non-comparative phase II study with 400mg of celecoxib with CapeOX group (C+ group) and CapeOX group (C- group) was conducted. Stratification factors were performance status 0/I, usage of low dose aspirin and institution. Primary endpoint is the appearance frequency of grade 2 or more vascular pain assessed using the Verbal Rating Scale (VRS) by a medical therapist who has no information about celecoxib administration. C- group patients who developed grade 2 or more vascular pain received celecoxib and were estimated with VRS. Results: Between October 2012 and February 2014, 81 patients were recruited from nine institutions in this study and randomly divided into two groups: 42 patients in C+ group and 39 patients in C- group. Grade II or more vascular pain rate was 55.3% in C+ group and 56.8% in C- group (p = 1.000). Fourteen patients in C- group who developed grade II or more vascular pain were given celecoxib and 50% of patients showed downgrading of vascular pain. Rate of grade II or more peripheral neuropathy was 36.6% in C+ group and 39.5% in C- group (p = 0.7916). Conclusions: Celecoxib has no prophylactic impact on either vascular pain or peripheral neuropathy. However, celecoxib effectively diminished vascular pain in patients with onset of grade II or more vascular pain. Clinical trial information: 000008814.