AIM: The aim is to compare the efficacy and safety of three different weight-adjusted intravenous erythropoietin (EPO) doses in patients with indirect traumatic optic neuropathy (TON). METHODS: This study is a multicentre, randomised, parallel-group, double-blind, dose-finding trial on patients aged ≥7 years with a confirmed diagnosis of indirect TON in ≤3 weeks. The trial had a 3-day treatment period and a 3-month follow-up period. Patients were randomly allocated (1:1:1) to receive EPO at doses of 900 IU/kg (300 IU/kg/day), 1800 IU/kg (600 IU/kg/day) or 3600 IU/kg (600 IU/kg/day on presentation and then 1 month later) EPO. The changes in the best-corrected visual acuity (BCVA), colour vision and relative afferent pupillary defect (RAPD) were assessed. RESULTS: Out of 118 eligible patients, 95 were randomised and 93 (31 in each group) completed the follow-ups. Three groups were not different regarding baseline BCVA (p=0.66), colour vision (p=0.25) and RAPD (p=0.79). All three groups showed a significant improvement of BCVA and RAPD with no significant differences among the groups. Colour vision showed a significant improvement only in the group with 3600 IU/kg EPO (p=0.005), even though final colour vision was not significantly different between the groups (p=0.49). Initial vision of no light perception (OR=7.79 (95% CI: 2.98 to 20.36), p<
0.001), older age (OR=4.76 (95% CI: 1.92 to 11.76), p<
0.001), longer trauma-treatment interval (OR=2.72, 95% CI: 1.16 to 6.33, p=0.02) and posterior orbital fractures (OR=2.63 (95% CI: 1.13 to 6.13), p=0.02) led to a significantly worse visual recovery. CONCLUSION: Increasing dose of EPO in patients with TON did not result in a better BCVA, colour vision and RAPD improvement. TRIAL REGISTRATION NUMBER: NCT03308448.