Background: Mitomycin C (MMC) is widely used, but the optimal dose and schedule have not been established. Objective: To evaluate the ablative power and patient safety of a short-term intensive schedule of intravesical MMC in patients with recurrent non-muscle-invasive bladder cancer (NMIBC). Design, setting, and participants: This was a prospective, single-center, nonrandomized study that compared 47 patients (group 1) with a history of low-to intermediate-risk NMIBC with long free-recurrence intervals, recurrence of <= 1 cm in maximum diameter, and negative cytology to 47 consecutive patients with the same baseline characteristics (group 2). Intervention: Intravesical MMC three times per week for 2 wk for group 1. Transurethral resection of bladder tumor (TUR-BT) and early instillation and a weekly schedule of intravesical MMC for group 2. All cancer-free patients underwent monthly MMC maintenance. Follow-up included bladder mapping, voiding and washing urinary cytology, TUR of suspected area, TUR of previous tumor location, and ultrasound or computed tomography/magnetic resonance imaging. Outcome measurement and statistical analysis: We used chi(2) and Student's t test for comparison of categorical and continuous variables, respectively. Kaplan-Meier curves were plotted to estimate cancer-free survival. The significance level was set to p < 0.05. Results and limitations: The complete response rate at 39 mo was 61.7% in group 1 and 70.2% in group 2 (p = 0.38). Kaplan-Mayer analysis revealed no difference in cancer-free survival rates overall (log-rank < 3.84), according to tumor size in each group (log-rank < 3.84), or between the groups (log-rank < 7.82). No cases of systemic toxicity were observed. Local toxicities did not differ between the groups (p = 0.32) and resolved on treatment of symptoms, and no patient discontinued their treatment. Limitations include the small number of patients, selection bias because of the single tertiary center, and short follow-up. Conclusions: The proposed MMC schedule had good ablative power that can be explained by better concordance between the scheduled timing and the tumor cell duplication rate. The short-term intensive schedule could be considered as a therapeutic strategy to replace TUR-BT in selected NMIBC patients. Patient summary: We report our experience of a tailored intravesical therapy schedule for bladder cancer. This schedule could be considered a therapeutic strategy to replace surgery for selected patients. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.