© 2015 American Brachytherapy Society. Purpose: High-dose-rate (HDR) brachytherapy alone is an effective treatment option for patients with early-stage prostate cancer. The purpose of this study was to quantify patient-reported short- and long-term toxicity and quality of life (QOL) after HDR monotherapy. Methods and Materials: Thirty-nine consecutive men between May 2001 and January 2012 were identified for this analysis. All patients underwent definitive HDR monotherapy for favorable prostate cancer to a total dose of 3150 cGy in three fractions, 3800 cGy in four fractions, or 3850 in five fractions. Patient-reported genitourinary function was assessed before HDR, during an acute period after treatment (within 90 days of HDR), and on long-term followup using the American Urological Association International Prostate Symptom Score, a urinary QOL Likert questionnaire, and the Sexual Health Inventory for Men questionnaire. Regression analyses were performed using the ordinary least squares method. Results: With median followup of 57 months, biochemical progression-free survival was 100%. There were no grade ≥3 toxicities. Dose to the urethra and bladder, as well as prostate size and intraprostatic urethra length were predictive for short-term changes in QOL. Advanced patient age was predictive for worse sexual function on both acute and long-term followup. Conclusions: Toxicity after HDR monotherapy for prostate cancer is acceptable. Patients with larger prostates, longer intraprostatic urethras, and greater doses to the bladder and urethra may experience worse acute urinary QOL. Older patients may experience greater impairment in sexual function in the short and long terms.