Background A recent noninferiority randomized trial showed that in terms of clinical effectiveness imiquimod was superior and topical fluorouracil noninferior to methylaminolaevulinate photodynamic therapy (MAL-PDT) for treatment of superficial basal-cell carcinoma (sBCC). Although it was expected that MAL-PDT would be more costly than either cream, a full cost-effectiveness analysis is necessary to determine the balance between effectiveness and costs. Objective To determine whether imiquimod or topical fluorouracil are cost-effective treatments for sBCC compared with MAL-PDT. Methods An economic evaluation was performed from a healthcare perspective. Data on resource use and costs were collected alongside the randomized clinical trial. The incremental cost-effectiveness ratio was expressed as the incremental costs per additional patient free of tumour recurrence. Results At 12 months follow-up, the total mean costs for MAL-PDT were (sic)680, for imiquimod cream (sic)526 and for topical fluorouracil cream (sic)388. Both imiquimod and topical fluorouracil were cost-effective treatments compared with MAL-PDT. Comparing costs and effectiveness of both creams led to a incremental investment of (sic)4451 to achieve an additional patient free of tumour recurrence. The acceptability curve showed that, for a threshold value of _ 4451, the probability of imiquimod being more cost-effective than topical fluorouracil was 50%. Conclusion Based on the 12 months follow-up results, imiquimod and topical fluorouracil cream are more cost-effective than MAL-PDT for treatment of sBCC. Hence, substituting MAL-PDT with either imiquimod or topical fluorouracil results in cost savings; these savings will be larger for topical fluorouracil. Longterm follow-up effectiveness data are necessary to confirm the cost-effectiveness of imiquimod vs. topical 5-fluorouracil cream.