This study evaluates risk factors for local tumour recurrence of main solid tumour, subretinal seed, vitreous seed and new tumour formation in eyes with retinoblastoma (RB) management with primary chemotherapy over 20 years of follow-up. The study included 960 eyes and 551 patients with RB management by primary chemotherapy. Ninety-five other eyes were excluded due to insufficient follow-up; 556 eyes of 408 patients developed some recurrence versus 313 eyes of 262 patients with no recurrence. Recurrence was more with younger mean age at presentation (10 versus 13 months) and with more advanced disease, greater number of tumours per eye, greater main largest tumour basal diameter and thickness, shorter mean tumour distance to foveola and optic disc and lower frequency of no subretinal seeds or fluid. Recurrence cases had more frequent requirement for additional globe-sparing treatment. Recurrence cases included 355 with main tumour recurrence, 244 with subretinal seeds, 162 with vitreous seeds and 118 with new tumour. Recurrence had more frequent need for enucleation. Most recurrence or new tumours were detected within the first three years of treatment. This study has identified those at greatest risk of recurrence. This is important as newer, targeted treatment can be implemented to treat most without enucleation.