Background: Non-muscle invasive bladder cancer (NMIBC) is associated with high rates of recurrence and progression despite adequate intravesical treatment with Bacillus Calmette-Guerin (BCG). Pembrolizumab was found to be effective in treating BCG-refractory NMIBC in the KEYNOTE-057 trial with a 41% complete response after 3 months and minimal adverse effects. As a result it was approved by the FDA on January, 2020, for the treatment of high risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors in patients ineligible for or unwilling to undergo cystectomy. This study reports a single institution’s experience using pembrolizumab in BCG refractory patients with high-risk NMIBC. Methods: Records of NMIBC patients who commenced treatment with pembrolizumab between January 2020 and January 2023 at a single institution were retrospectively reviewed. Demographic and clinicopathologic information was collected. Kaplan-Meier curves were generated to calculate progression-free survival (PFS), and treatment-specific survival (TSS). The combined positive score (CPS) of PD-L1 was assessed for each case treated by pembrolizumab. Results: Out of 250 patients with NMIBC who were screened for the study, 18 met the inclusion criteria. The median age was 74.1 years (IQR=67.8 – 81.4), male to female ratio of 3.5:1. The median follow-up time was 17.5 months (IQR= 8.1–22.5). A previous history of CIS was present in all patients as well as second-line chemotherapy for BCG refractory disease. At the start of pembrolizumab, stage distribution was as follows: 1 (5.6%) cTa, 6 (33.3%) had CIS, and 11 (61.1%) cT1. After an average of 8.9 cycles, 72.2% (13/18) stopped treatment. 27.8% (5/18) are still undergoing treatment, with an average of 12.6 cycles (SD=10.4). 1 out of the 13 patients who stopped treatment had a complete response. The remaining reasons for termination of treatment are Grade 2 or higher immune-related adverse events in 53.8% (7/13), progression in 30.8% (4/13), and recurrence in 7.7% (1/13). Four patients ultimately required radical cystectomy which revealed 1 pTa, 1 pTis, 1 pT1, and 1 pT4. Only 1 patient had CPS of PD-L1 > 10. Conclusions: There were higher rates of toxicity from pembrolizumab for the treatment of BCG-refractory NMIBC than expected. More research is needed to better define the patients who are likely to benefit from this treatment. Pembrolizumab for BCG refractory NMIBC can have high rates of Grade 2 or higher adverse events leading to early withdrawal from treatment. Early discussion about radical surgery remains an important part of the treatment guidelines for BCG refractory NMIBC.