Background: Bacillus Calmette-Guerin (BCG) is currently recommended as adjuvant therapy following complete transurethral resection of bladder tumor (TURBT) for high-risk non-muscle invasive bladder cancer (NMIBC). However, continued BCG production shortages have precluded the use of BCG in many urologic practices. Efficacy of sequential intravesical gemcitabine and docetaxel (Gem/Doce) in the BCG failure setting has been reproduced across multiple institutions. In response to the continuing BCG shortage, Gem/Doce has been utilized at our institution in the BCG-naïve setting. We report the outcomes of a large cohort of patients with high-risk BCG-naïve NMIBC treated with Gem/Doce. Methods: We retrospectively identified all patients with BCG-naïve high-risk NMIBC who were treated with Gem/Doce from May 2013 through April 2021. We included patients with intent to receive 6 weekly intravesical instillations of sequential 1 gram gemcitabine and 37.5mg docetaxel after complete TURBT. Monthly maintenance of 2 years was initiated if disease free at first follow-up. The primary outcome was recurrence-free survival (RFS) and efficacy was evaluated in an intention-to-treat manner. Recurrence was defined as pathologically confirmed tumor relapse in the bladder or prostatic urethra. Progression was defined as T-stage increase from Ta or CIS to T1 or development of muscle invasive or metastatic disease. Survival was assessed using the Kaplan-Meier method and log rank test, indexed from the first Gem/Doce instillation. Results: One hundred seven patients with median follow-up of 15 months were included in the analysis. There were 47 with any CIS, 55 with T1 disease, and 7 with micropapillary variant histology. Four patients did not complete a full induction cycle due to hematuria (3) and severe frequency/nocturia (1). 19 patients sustained a recurrence at any point during follow-up. RFS was 89%, 85%, and 82% at 6, 12, and 24 months, respectively. No difference in RFS was seen in patients with or without CIS (p = 0.42). No patients met criteria for either form of disease progression. One patient underwent cystectomy due to end-stage lower urinary tract symptoms, with final pathology pTisN0. No patients died of bladder cancer. Overall survival was 84% at 24 months. 46 patients reported any symptoms during treatment. Common side effects included urinary frequency/urgency (36%), hematuria (11%), and dysuria (8%). Conclusions: In a large cohort of high-risk, BCG-naïve NMIBC patients, Gem/Doce showed excellent efficacy (84% 2-year HG-RFS). These rates are similar to modern treatment naïve cohorts receiving BCG. Prospective comparative analysis of Gem/Doce in BCG-naïve populations is warranted.