Background: We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer who had persistent or recurrent disease after prior intravesical therapy with BCG. The International Prostate Symptom Score (IPSS) were administered to assess subjects’ urinary bother during the trial. Methods: Eighteen subjects were consented for the study, 13 were treated. The study population was comprised of 11 males, 2 females, with age range 42 - 92 years. The IPSS was assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and at 3 and 6 months from treatment completion. IPSS outcomes were analyzed using a mixed-model repeated measures analysis with p-value < 0.05 considered statically significant. Results: For each time point, there was no significant change in any of the component variables of the IPSS. There was no increase in reported bother symptoms over the course of treatment, given median IPSS scores of 9, 11, 7, and 8 (IQR 1.75) for each time point, respectively. Furthermore, quality of life measurements demonstrated no significant change in subjective burden with 75% of subjects reporting that they were “mostly satisfied” with treatment outcomes, followed by 13% reporting “delighted” or “pleased” at 6 month follow-up. Conclusions: There is no significant change in quality of life or the perceived bother of symptoms indicated in the component variables of the IPSS for our study population before, during or after treatment.