To quantify the duration of anesthesia required for optimal management of retinoblastoma (Rb), stratified by clinical factors. The medical records of Rb patients treated at Phoenix Children's Hospital between January 2011 and January 2022 were reviewed retrospectively. Demographic, tumor, and treatment data were collected. Anesthesia time was recorded for procedures requiring general anesthesia, including intra-arterial chemotherapy (IAC), enucleation, brainstem auditory evoked response testing (BAER), port placement, magnetic resonance imaging (MRI), and examination under anesthesia (EUA). Descriptive statistics were used to summarize patient and clinical characteristics. Total anesthesia time was 48,991 minutes for 610 procedures in 43 patients. The median follow-up time was 36 months (range, 12-114 months). Average anesthetic durations per exposure were 274, 152, 81.8, 62.5, 60.7, and 45 minutes for IAC, enucleation, BAER, port placement, MRI, and EUA, respectively. Patients with bilateral Rb underwent a median of 1,659 minutes of total anesthesia, compared with 397 minutes for those with unilateral disease. In patients with unilateral Rb, median total anesthesia time was 2,651, 1681, 312, 397 minutes for International Classification of Retinoblastoma grades B, C, D, and E tumors, respectively. Patients who received IAC as their primary treatment had the highest median anesthesia duration (2,100 minutes), followed by systemic chemo (654 minutes) and enucleation (289 minutes). Treatment of Rb requires prolonged and repeated exposure to general anesthesia. Future studies are required to determine the potential effects of these childhood anesthetic exposures.