This is a retrospective medical records review of 50 patients (54 eyes) with retinoblastoma (RB), who received I-125 episcleral plaque brachytherapy (EPBRT) prior to (primary) or following chemoreduction (delayed) alone and in combination with non-irradiative focal therapy. Fifty-six plaques were used between 1986 to 2010, with a median follow-up of 8.3 years. The median time from diagnosis to plaque placement was 12.7 months. Treatment failure was defined as the need for subsequent external beam radiation (EBRT) and / or enucleation. Cumulative incidences (CI) and 95% CI of treatment failure and enucleation following EPBRT at five years was 37% and 42.2% respectively. The absence of prior diode or green laser therapy was predictive of increased risk for treatment failure (p=0.02 and 0.03). The authors concluded that the use of any focal treatment was not predictive of time to treatment failure (p=0.33) or the need for EBRT to achieve successful salvage. International Classification C or D was predictive of decreased time to enucleation (p=0.004).