This a single centre retrospective review of consecutive patients between 1997 and 2014, of all sporadic unilateral retinoblastoma (RB) group D cases, treated with combined intravenous chemotherapy (IVC) and focal treatments (1997- 2008), or intra-arterial chemotherapy (IAC) treatment (2008 to 2014), as primary treatment. Mean follow-up; 23 patients had 105.3 months in the IVC group and 25 patients had 41.7 months in the IAC group respectively. The treatment duration was much shorter significantly in the IAC group (p<0.001). Ten eyes in the IVC group had enucleation. Final visual acuity (VA) was significantly better in the IAC group. In the IVC group, one eye had no perception of light (PL) and the remaining 12 eyes‘ median (VA) at last visit was 1.4 logMAR. In the IAC group, 22/25 eyes had (PL) or better; median VA was 0.9 logMAR, (p<0.01). No extraocular disease, metastasis or long-term systemic complications were detected in either group. Eight patients in the IVC group had transfusions and four in the IAC group had transient cardiorespiratory disturbances. Four eyes in the IVC receiving brachytherapy had developed radiation-induced retinopathy. Three eyes in the IAC group developed occlusive choroidopathy and three eyes had Melphalan-related retinopathy. The authors concluded that the IAC group will have a shorter treatment period, better ocular survival and VA than the IVC group as first line treatment.