Background: The efficacy of an immediate single chemotherapy instillation after transurethral resection of a bladder tumour (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC) remains a topic of debate. Evidence is even more scarce when an immediate instillation is followed by adjuvant instillations. Objective: To compare the effect of a mitomycin C (MMC) instillation within 24. h to an instillation 2 wk after TURBT in patients with NMIBC with or without adjuvant instillations. Design, Setting, and participants: Between 1998 and 2003, 2844 NMIBC patients were randomised for immediate versus delayed MMC instillation after TURBT. Patients were categorised in low-risk (LOR), intermediate-risk (IMR), and high-risk (HIR) groups. Total numbers of instillations in these groups were 1, 9, and 15, respectively. Outcome measurements and statistical analysis: Primary end point was 3-yr recurrence risk for the IMR and HIR groups and 5-yr risk for the LOR group. Secondary outcomes were time to recurrence and incidence of adverse events. Analyses were performed with the log-rank test, Cox-regression, and χ2 test in SPSS. Results and limitations: A total of 2243 patients were eligible on an intention-to-treat basis. Recurrence risks were 43% and 46% in the LOR group (5-yr follow-up, p = 0.11), 20% and 32% in the IMR group (3-yr follow-up, p = 0.037), and 28% and 35% in the HIR group (3-yr follow-up, p = 0.007), for an immediate and a delayed instillation, respectively. For all patients, the recurrence risk was 27% (95% confidence interval [CI], 24-30) in the immediate and 36% (95% CI, 33-39) in the delayed instillation group (p <. 0.001) with a 27% reduction in relative recurrence risk (hazard ratio: 0.73, 95% CI, 0.63-0.85, p <. 0.001). The incidence of adverse events did not differ significantly between treatment groups (immediate instillation 25%, delayed instillation 22%, p = 0.08). The risk groups in our study differ slightly from the current guidelines, which is a limitation of our study. Conclusions: An immediate, single instillation after TURBT reduces the recurrence risk in NMIBC patients, independent of the number of adjuvant installations. Patient summary: A single instillation of chemotherapy after the resection of non-muscle-invasive bladder cancer reduces the recurrence risk, even if patients are treated with an adjuvant schedule of instillations. An intravesical instillation with mitomycin C within 24. h after transurethral resection of a bladder tumour reduces the risk of recurrence in non-muscle-invasive bladder cancer patients, independent of the number of adjuvant installations.