Purpose To evaluate the efficacy of 106Ru plaque brachytherapy for the treatment of retinoblastoma. Methods and Materials We reviewed a retrospective, noncomparative case series of 39 children with retinoblastoma treated with 106Ru plaques at the Jules-Gonin Eye Hospital between October 1992 and July 2006, with 12 months of follow-up. Results A total of 63 tumors were treated with 106Ru brachytherapy in 41 eyes. The median patient age was 27 months. 106Ru brachytherapy was the first-line treatment for 3 tumors (4.8%), second-line treatment for 13 (20.6%), and salvage treatment for 47 tumors (74.6%) resistant to other treatment modalities. Overall tumor control was achieved in 73% at 1 year. Tumor recurrence at 12 months was observed in 2 (12.5%) of 16 tumors for which 106Ru brachytherapy was used as the first- or second-line treatment and in 15 (31.9%) of 47 tumors for which 106Ru brachytherapy was used as salvage treatment. Eye retention was achieved in 76% of cases (31 of 41 eyes). Univariate and multivariate analyses revealed no statistically significant risk factors for tumor recurrence. Radiation complications included retinal detachment in 7 (17.1%), proliferative retinopathy in 1 (2.4%), and subcapsular cataract in 4 (9.7%) of 41 eyes. Conclusion 106Ru brachytherapy is an effective treatment for retinoblastoma, with few secondary complications. Local vitreous seeding can be successfully treated with 106Ru brachytherapy.