BACKGROUNG: Keloids are a common problem and can be challenging to treat. Intralesional triamcinolone has been the mainstay of therapy. However, recurrence rates are significant and steroids may have adverse effects such as hypopigmentation. Recently there have been occasional reports in the literature on the use of antineoplastic agents in keloid therapy. The purpose of this study is to evaluate the efficacy of a 5-fluorouracil/steroid mixture over the past seven years and compare the results with steroid treatment alone. METHODS: All charts from 1999 to 2006 were reviewed for patients who received either a combination of 5-FU and triamcinolone or steroid alone. The follow-up period ranged from 6 months to 6 years. A mixture of 75% 5-fluorouracil and 25% triamcinolone was most commonly used. Percentage reduction in lesion size and adverse effects were evaluated. RESULTS: A total of 94 patients with 102 keloids were identified. The 24 patients who underwent excision with the 5-FU/steroid combination had a 92% average reduction in lesion size compared with 73% in the 26 patients who did not receive 5-FU. The 52 patients who received 5-FU and steroid without excision had an average size reduction of 81%. These differences were statistically significant (p = 0.05). Those patients who received treatment with 5-FU/steroid combination had a 21% incidence of adverse effects compared with 15% in the steroid only group. However, this difference was not statistically significant. CONCLUSION: The results of this study suggest that combination 5-FU/steroid may be superior to traditional therapies without any statistically significant difference in adverse effects. The successful use of 5-FU in patients who failed treatment with triamcinolone is particularly significant. Prospective trials using antineoplastic agents are needed in keloid research.