Objective To evaluate the efficacy of surgery, chemotherapy and surgery combined chemotherapy for retinoblastoma (RB), and analyze the prognostic factors of RB patients. Methods Clinical data of 1188 RB patients registered in the Surveillance, Epidemiology and End Results (SEER) database from January 2000 to December 2019 were retrospectively analyzed. The baseline characteristics of patients treated with surgery, chemotherapy or surgery combined with chemotherapy were balanced by inverse probability of treatment weighting (IPTW). Log-rank test analysis was used to compare the survival probability of patients in the 3 groups, and Cox regression models were used to analyse the factors influencing the prognosis of RB patients. Results A total of 1188 RB cases were included in this study, including 426 cases in surgery group, 200 cases in chemotherapy group and 562 cases in surgery combined with chemotherapy group. After IPTW weighting, baseline data such as age, sex and race were balanced (P>0.05). Log-rank test results showed that the survival curves of the three groups were significantly different before and after weighting (P<0.05). After weighted, the survival of patients in surgery group was significantly better than that in chemotherapy group and surgery combined chemotherapy group (P<0.05), and there was no statistical significance between chemotherapy group and surgery combined chemotherapy group (P>0.05).The weighted patient survival probability at 1st, 3rd and 5th years were 99.7%, 98.9% and 98.6% in surgery group; 97.4%, 95.8% and 95.8% in chemotherapy group; and 97.9%, 95.8% and 95.0% in surgery combined chemotherapy group. Cox regression analysis showed that compared with surgery group, the specific risk ratio of death was 1.367 (95%CI 1.100-1.700) in chemotherapy group and 1.132 (95%CI 0.963-1.330) in combined chemotherapy group. Compared with patients with 1 RB lesion, the patient-specific mortality risk ratio for patients with 2 or more RB lesions was 0.399 (95%CI 0.268-0.594). Conclusions Patients with RB have higher survival rates probability after treatment. After controlling the influence of age, sex and other factors, the effect of surgery was better among the three treatment methods. Multifocality may be an independent prognostic factor in RB patients.