The treatment of keloids remains unsatisfactory. Intralesional 5-fluorouracil (FU) has not been much investigated as a monotherapy in the treatment of keloids. We sought to evaluate the use of intralesional injections of 5-FU in the treatment of keloids. A total of 20 patients (11 male and 9 female) were treated once weekly with intralesional injections of 5-FU (50 mg/mL). Patients received an average of 7 treatments. Average injection volumes were 0.2 to 0.4 mL/cm 2. All patients had full blood cell count, liver function tests, and renal function tests before and after treatment was commenced. A total of 10 patients had biopsy specimens taken before starting treatment as a baseline and after 6 sessions. Routine hematoxylin-eosin and immunohistochemical analysis detecting Ki-67 and transforming growth factor-β were performed on paraffin sections. All patients were followed up for 12 months, or until recurrence was noted. Of 20 patients, 17 (85%) showed more than 50% improvement. Only one did not respond favorably. Small and previously untreated lesions improved the most. Pain (20 of 20), hyperpigmentation (20 of 20), and tissue sloughing (6 of 20) were the main adverse effects. Histopathologic and immunohistochemical evaluation were consistent with the clinical observations. Ki-67 proliferative index was significantly reduced ( P = .0001) after treatment. Transforming growth factor-β was reduced less significantly. Recurrence was noted in 47% (9 of 19) of patients who responded to treatment within 1 year. A correlation was found ( P = .028) between the duration of the lesions and recurrence. Our study demonstrates that intralesional 5-FU may be effective in the treatment of keloids, but recurrence is common and further investigation is required.