Purpose: To evaluate the direct costs and analyze the potential cost-driving factors in the first year of retinoblastoma treatment in China. Methods: Sixty-nine pediatric patients who received multidisciplinary treatment for retinoblastoma in three tertiary hospitals from 2006 to 2011 were included in this retrospective study. The direct costs, including costs for chemotherapy, focal therapy, anesthetic procedure, enucleation, fundus examination, hospitalization and outpatient appointment, transportation, and accommodation for family members, were obtained from medical records and interviews. Results: The average direct costs for retinoblastoma treatment was U.S. $9,422 +/- 3,709 per patient during the first year. Of this amount, chemotherapy-related expenses were $2,991 +/- 3,083 (31.74%), transportation and accommodation expenses were $2,560 +/- 1,348 (27.17%), general anesthetic procedure was $1,081 +/- 2,711 (11.48%), and enucleation was $900 +/- 1,015 (9.56%). The costs for intra-arterial chemotherapy ($1,224 +/- 754) and chemotherapy drugs ($517 +/- 134) were major components in chemotherapy-related expenses. The retinoblastoma clinical stage and family income positively correlated with the total direct costs (P = .0358 and .0185, respectively). Conclusion: Comprehensive treatment involving chemotherapy imposes an enormous economical burden on families affected by retinoblastoma in China. [J Pediatr Ophthalmol Strabismus 2012;49:353-358.]