Background: Acupuncture can reduce pain and urinary urgency and frequency. Treatment-related dose-limiting dysuria and irritative bladder symptoms are common in patients receiving intravesical Bacillus Calmette-Guerin (BCG) for the treatment of non muscle-invasive bladder cancer (NMIBC). We evaluated the feasibility, safety, and tolerability of weekly in-clinic pre-procedure acupuncture among patients receiving induction BCG. Methods: Patients with high-risk NMIBC undergoing induction BCG were randomized 2:1 to a standardized acupuncture protocol (Acu) or an attention waitlist control. Acu patients received acupuncture prior to each of 6 weekly BCG instillations. Feasibility was assessed via recruitment, retention, and intervention adherence. Acupuncture safety and tolerability were assessed via physician-reported CTCAE v5.0 and adverse events (AEs). Secondary endpoints included BCG treatment adherence, patient-reported BCG-related toxicity, and bladder cancer-specific and generic quality of life (QOL), assessed with the EORTC-QLQ-NMIBC-24 and -C30 surveys. Subjective assessments of acupuncture acceptability were assessed through patient exit surveys. Results: Between 1/21 and 7/22, 43 patients were randomized to Acu (n=28) vs. Control (n=15). Median age was 70.3 years and 76% were male. Week 7 follow-up surveys were completed by 93% of patients; 6 patients withdrew early due to disease progression, refractory gross hematuria, or for patient preference. Acupuncture was successfully delivered prior to each BCG treatment in Acu patients with no acupuncture-related AEs or interruptions to induction BCG. BCG-attributed AEs were reported by 91% Acu and 100% Control patients, including pain (28% vs. 43%, respectively, p=0.34) and urinary symptoms (62% vs. 79%, respectively, p=0.31). Comparing Acu with Controls, change in QOL over the study period demonstrated greater improvements in median urinary symptoms (9.5, IQR 0.0-19.0 vs. 0.0, IQR -14.3-7.1, p=0.02) and a trend towards improvement in median pain scores (16.7, IQR 0.0-16.7 vs. 8.3, IQR 0.0-33.3 p=0.68) among patients in the Acu arm. 96% of Acu patients reported that acupuncture was “very/extremely helpful” and 91% would recommend acupuncture to other patients. Conclusions: Acupuncture prior to induction BCG treatments is feasible and safe. In this Phase I/II trial, we observed reductions in pain and a trend towards improved urinary function scores over successive treatments among patients undergoing in-clinic pre-BCG instillation acupuncture. Patients receiving acupuncture reported high degrees of satisfaction with treatments. Future larger randomized controlled trials are needed to further characterize the efficacy of acupuncture with respect to pain, urinary symptoms and impact on QOL, and continuation of maintenance therapy during BCG treatment. Clinical trial information: NCT04496219.