Background: Solid evidence of the safety and effectiveness of retinoblastoma (RB) conservative treatment using thermotherapy and systemic chemotherapy with long-term follow-up is scarce, especially in low-resource countries. Aims: This study examined the outcomes of this treatment and associated predictors in Vietnam to strengthen the current RB treatment protocol focusing on preserving eye and vision in low-resource settings. Methods and results: A prospective cohort study was conducted at Ho Chi Minh City Eye Hospital in Vietnam from 2005 to 2019. All eligible patients with bilateral RB (one eye already removed and another eye classified as group A or B) and without previous treatment were recruited. All patients received thermotherapy and six cycles of systemic three-agent chemotherapy repeated every 4 weeks. A standardized questionnaire was used to collect information on study participants' age, symptoms, tumor characteristics, treatment, and outcomes. Among 50 eyes of all 50 patients with a median age of 9 (4–20) months, 34 eyes were in group B (68%). The median follow-up time was 60 (60–84) months. All 139 preserved tumors regressed mostly to type 4 (70.4%) and type 3 (23.7%) scars. Kaplan–Meier analysis found the overall globe-salvage rate at 5 years of 91.9% (95% CI: 80.1%–97.7%). Most eyes (41/50, 82%, 95% CI: 69.2%–90.2%) had a final visual acuity ≥0.1. The visual acuity is higher when tumors regressed to a type 4 scar (p =.007, AOR = 8.098, 95% CI: 1.79–36.53) which also shows less enucleation than a type 3 scar (p =.002, AOR = 0.06, 95% CI: 0.01–0.37%). Gender effect on visual acuity after treatment was significant and may be due to discrimination. No major complications were recorded. Conclusion: Conservative treatment of early-stage RB is safe and effective. Long-term, thorough follow-ups of patients post-treatment are needed. The regression patterns of scars could be a useful indicator of treatment failure.@en