PURPOSE: Globally, disparities exist in retinoblastoma treatment outcomes between high- and low-income countries, but independent analysis of American countries is lacking. We report outcomes of American retinoblastoma patients and explore factors associated with survival and globe salvage. DESIGN: Subanalysis of prospective cohort study data. METHODS: Multicenter analysis at 57 American treatment centers in 23 countries of varying economic levels (low income [LIC], lower-middle income [LMIC], upper-middle income [UMIC], and high income [HIC]) of 491 treatment-naïve retinoblastoma patients diagnosed in 2017 and followed through 2020. Survival and globe salvage rates analyzed with Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Of patients, 8 (1.6%), 58 (11.8%), 235 (47.9%), and 190 (38.7%) were from LIC, LMIC, UMIC, and HIC groups, respectively. Three-year survival rates in LICs were 60.0% (95% confidence interval [CI] 12.6-88.2) compared with 99.2% (95% CI 94.6%-99.9%) in HICs. Death was less likely in patients >4 years of age (vs ≤4 years, HR = 0.45 [95% CI 0.27-0.78], P = .048). Patients with more advanced tumors (eg, cT3 vs cT1, HR = 4.65 × 109 [95% CI 1.25 × 109-1.72 × 1010], P < .001) and females (vs males, HR = 1.98 [95% CI 1.27-3.10], P = .04) were more likely to die. Three-year globe salvage rates were 13.3% (95% CI 5.1%-25.6%) in LMICs and 46.2% (95% CI 38.8%-53.3%) in HICs. At 3 years, 70.1% of cT1 eyes (95% CI 54.5%-81.2%) vs 8.9% of cT3 eyes (95% CI 5.5%-13.3%) were salvaged. Advanced tumor stage was associated with higher enucleation risk (eg, cT3 vs cT1, subhazard ratio = 4.98 [95% CI 2.36-10.5], P < .001). CONCLUSIONS: Disparities exist in survival and globe salvage in American countries based on economic level and tumor stage demonstrating a need for childhood cancer programs.