Background: Retinoblastoma (RB) is a malignant intraocular tumor diagnosed in early childhood that requires extensive medical and surgical treatment at a young age. Health-related quality of life (HRQOL) is thought to be diminished due to visual impairment, facial deformities, and fear of recurrence or secondary cancer. However, few studies have identified variables associated with HRQOL among those with RB. Purpose: To compare HRQOL of adolescents and young adults (AYAs) with RB to matched controls and to identify predictors of HRQOL in RB survivors. Methods: Using a cross-sectional design, 198 AYAs (101 RBs and 97 controls) completed HRQOL (PROMIS®-29 profile) and psychosocial questionnaires (Rosenberg self-esteem scale, multidimensional scale of perceived social support, and Hollingshead index for socioeconomic status). Clinical variables (age at diagnosis, visual acuity, laterality, heredity, treatment regime, and anesthesia exposure) were extracted from the medical record. Correlates of HRQOL were estimated using linear regression models. Results: RB survivors reported similar HRQOL compared to controls. Physical function ( p < .001), social support ( p = .013), and self-esteem ( p = .028) were lower in the RB group compared to controls. Visual acuity and self-esteem accounted for 52% of the variance in PROMIS physical health summary scores and self-esteem accounted for 38% of the variance in mental health summary scores. Conclusion: Despite deficits in physical function and self-esteem HRQOL in RB survivors was comparable to healthy counterparts. However, the majority of RB survivors in this study had normal visual acuity. Clinicians should explore ways to enhance self-esteem in RB survivors.