This is the first reported randomised clinical trial comparing methotrexate versus mycophenolate mofetil (MMF) for the treatment of non-infectious intermediate uveitis, posterior uveitis or panuveitis. To be eligible for recruitment, patients had to be on ≥15mg oral prednisone and demonstrated a previous history of steroid taper failure. Additionally, the patients should not have had any previous exposure to immunosuppressants, intraocular surgery in the past 30 days, fluocinolone acetonide implant surgery in the past three years, and periocular or intravitreal corticosteroid injection in the past 90 days. A total of 80 patients were randomised to either 25mg a week oral methotrexate or 1g twice daily oral MMF. If the medication was not tolerated, patients were allowed to adjust their study dose. Sixty-seven patients (35 methotrexate; 32 MMF) completed the six month study period. There were no statistically significant differences in terms of the time to steroid-sparing control of inflammation, change in best-corrected visual acuity, resolution of macular oedema, adverse events, or tolerability. Treatment success was achieved in 69% of methotrexate patients and 47% of MMF patients, but this difference did not achieve statistical significance (P=0.09). The results from this study seem to contrast with that from other retrospective studies, and is likely to have cost implications due to the significantly higher price of MMF.