Non-muscle-invasive bladder cancer (NMIBC) can be treated using transurethral resection (TUR), but high incidence of intravesical recurrence remains a clinical challenge. Single immediate postoperative instillation of chemotherapy (IPIOC) is controversial for NMIBC patients with intermediate recurrence risk. The aim of the present study was to report the efficacy and toxicity of IPIOC, particularly in intermediate-risk NMIBC patients, in the real-world setting. We retrospectively analyzed 363 consecutive patients with primary NMIBC who underwent radical TUR at Kyoto University Hospital between 2007 and2016. In low-risk patients, recurrence-free survival (RFS) was significantly better for IPIOC than non-IPIOC (2-year RFS: 89.3% vs. 59.4%; P= .001). In intermediate-risk patients, IPIOC was associated with significantly longer RFS compared with non-IPIOC (2-year RFS: 85.5% vs. 58.2%; P= .011). IPIOC and bacillus Calmette-Guérin (BCG) were independent predictors for post-TUR recurrence (non-IPIOC vs. IPIOC: hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.14-4.88; P= .02; non-BCG vs. BCG: HR, 2.22; P= .045, 95% CI, 1.02-5.30). In the high-risk group, only BCG was an independent prognostic factor of recurrence in a multivariate Cox proportional hazards model (HR, 2.55; P= .006, 95% CI, 1.32-4.87). There were no significant differences between the BCG-only group and the IPIOC with BCG group in Grade 3 or more local (16 patients [21%] vs. 21 patients [24%]; P= .61) or systemic (3 patients [4%] vs. 6 patients [7%]; P= .40) toxicity rates. Our study showed the efficacy of IPIOC for the prevention of intravesical recurrence in primary intermediate-risk NMIBC patients regardless of BCG therapy.