This single blinded randomised controlled trial (RCT) compared 43 patients with 50 symptomatic keloids were were randomised to two matched groups of 25 scars, receiving either flurouracil (5-FU) or current first-line treatment, triamcinolone (TAC). The surgeon administering the injectable treatments was unblinded, whilst the clinical observer and analysis were performed in a blinded manner. The primary endpoint was remission of keloid at six months after treatment (flattening where no further injections were feasible or needed). Secondary endpoint assessments included physician and patient assessment of keloid scar cosmesis (using the patient and observer scar assessment score), and spectrocutometry on punch biopsy specimens in order to assess blood vessel density, change in haemaglobin (Hb) concentration and fibroblast proliferation (used as surrogate markers for ongoing metabolic scar activity). In addition, there was clinical assessment of adverse effects such as skin atrophy / telangietasia. Follow-up occurred five times, at three to four weekly intervals until six months. Treatment efficacy did not differ significantly (p<0.05) between the two groups (46% remission in 5-FU vs. 60% in the TAC group), and similarly the POSAS evaluation (both patient and observer) decreased in the 5-FU and TAC groups (<0.05), with no difference seen between them. However, there was a significantly greater incidence of adverse outcomes with TAC resulting in greater rates of skin atrophy (44% in TAC vs. 8% in 5-FU) and telangietasia (50% in TAC vs. 21% in 5-FU), whilst 5-FU caused some immediate local blistering in one patient and hyperpigmentation in three others. There were other differences in secondary endpoints, that the estimated Hb concentration fell in the TAC group, but not 5-FU, and the blood vessel density decreased with TAC treatment but not significantly in 5-FU. The proliferation rate (measured by Ki-67 values) decreased in the TAC group but increased in the 5-FU group. Vascular density (measured by CD31) decreased in the TAC group but not in the 5-FU group. This may suggest a differing mechanism of action for keloid scar regression between the two treatments. Whilst TAC treatment has been well established since the 1970s, 5-FU treatment for keloid scars is considered more experimental. Previous reports from observational studies have documented 70-95% success rates. In this study, 5-FU showed no clear clinical benefit over TAC, and approximately 50% of keloids in each group didn’t respond to treatment that further research into novel treatments for keloids are still needed, and progression to other keloid treatment strategies may be reasonable after a six month trial of injectable therapy.