Background: Pediatric rhabdomyosarcoma (RMS) is commonly cured with chemotherapy and radiation. However, late effects of radiotherapy (RT) can be disabling. Proton RT irradiates less normal tissue, which should result in fewer late side effects of treatment. The purpose of this study was to describe the disease control and side effect profile of proton RT in RMS patients (pts). Methods: Eligible pts included those with localized disease and metastatic embryonal RMS if age 2-10. All pts were treated with VAC (vincristine, actinomycin, cyclophosphamide) based chemotherapy and proton RT, median dose 50.4 Gy (36-50.4 Gy_RBE). Concurrent enrollment in COG protocols was allowed. All pathology/imaging was reviewed at the treating institution. Results: 47 pts with RMS were prospectively enrolled from January 2005 to June 2011 and evaluable for analysis. Median age was 3.1 yrs, (range 0.6-15.6 years; M/F ratio 23:24). There were 1, 7, 37, and 2 Group I, II, III and IV and 14, 12, 19 and 2, Stage I-IV pts respectively, and 33 with embryonal 14 with alveolar/other. Most common sites included PM (48.9%), orbital (23.4%) bladder/prostate (6.4%), H&N non-PM (6.4%), extremities (4.3%), trunk/abdomen 2.1%), perineal/anal region (2.1%) and other (6.4%). Median follow-up is 15.2 months. One/two-year overall survival (OS) and progression-free survival (PFS) for the entire group is 94/81% (OS) and 79/73% (PFS). 2-year OS for stage I,II/III,IV pts is 91/66% (OS, p=0.114) and two-year PFS for these pts is 86/57%, respectively, (p=0.083. 16 (34%) had grade 3/4 acute toxicities attributable to the radiation during treatment, the most common of which was mucositis/oral pain (12.8%), anorexia (4.3%), and erythema (4.3%). Among the 24 pts analyzable for late toxicities with at least 2 yrs of follow up, there were no grade 3 or 4 late toxicities attributable to radiation. Conclusions: Early results of this prospective trial demonstrate comparable disease outcomes and thus far limited late effects in a young pediatric RMS population. However, additional follow up is needed to determine if protons truly reduce rates and severity of late effects compared with photon cohorts published in the literature.