Abstract Purpose To evaluate the safety and efficacy of pars plana vitrectomy (PPV) for recalcitrant vitreous seeding from retinoblastoma and concurrent retinal detachment. Methods In this retrospective interventional case series, intravitreal chemotherapy-assisted PPV was performed in 6 patients with persistent retinoblastoma vitreous seeds and concurrent retinal detachment. Globe salvage, retinal reattachment, and visual preservation at last follow-up visit were calculated. Results Six eyes, initially classified as group D (n=4) or E (n=2) with sphere and (or) cloud vitreous seeds, received standard systemic with intravitreal chemotherapy and subsequently developed refractory vitreous seeds with concurrent retinal detachment. PPV produced complete elimination of vitreous seeds in all 6 eyes and no vitreous seeding recurred over a mean follow-up of 29.6 months. Globe salvage and complete retina reattachment were attained in all 6 eyes (100%). Last follow-up vision acuity was assessable in 4 eyes with 80% (3/4) better than 0.4. Three eyes (50%) received repeated systemic or focal treatment because of the recurrent retinal tumor. There was no case of extraocular tumor extension or systemic metastasis. Conclusion Administration of intravitreal chemotherapy-assisted PPV appears to be a safe and effective alternation for the initial treatment of refractory vitreous seeds from retinoblastoma. It is also a promising therapeutic strategy to repair concurrent retinal detachment and preserve the remaining visual function.