Purpose: To evaluate the safety and efficacy of multimodality treatment with vincristine, actinomycin-D, and cyclophosphamide (VAC) therapy, surgery, and radiotherapy according to the U.S. Intergroup Rhabdomyosarcoma Study IV (IRS-IV), and to establish a central review system and standard treatment for intermediate-risk pediatric rhabdomyosarcoma in Japan. Patients and methods: The JRS-I was a single-arm, phase II trial for intermediate-risk rhabdomyosarcoma treatment with open enrollment from June 2004 to March 2009. Patients received 12 cycles of VAC every 3 weeks for 42 weeks, with local therapy beginning after week 12. The endpoints were progression-free survival (PFS), overall survival (OS), and incidence of hepatic veno-occlusive disease (VOD). Results: Thirty-one eligible patients were enrolled, and at a median follow-up of 5.2 years, the 3-year PFS and OS for patients were 74.2% ± 7.9% (95% CI 55.0%-86.2%) and 90.3% ± 5.3% (95% CI 72.9%-96.8%), respectively. VOD occurred in 3 (8%) of the 40 evaluable patients, but all recovered, and there were no deaths. Conclusion: The VAC regimen for intermediate-risk rhabdomyosarcoma with the first central review system in Japan is safe and feasible, and these findings can be positioned as basic data for improving treatment outcomes in Japan.