Introduction: To identify differences in acute urinary and sexual toxicity between a 6-fraction and 2-fraction high-dose-rate brachytherapy monotherapy regimen and correlate dosimetric constraints to short-term toxicity. Methods: A single institution retrospective study of 116 men with prostate cancer treated with HDR monotherapy from 2010 to 2015 was conducted. Eighty-one men had 7.25 Gy 9 6-fractions and 35 men had 13.5 Gy 9 2-fractions. Patients had two CT-planned implants spaced 1-2 weeks apart. Patient baseline characteristics, International Prostate Symptom Scores (IPSS) and Sexual Health Inventory for Men (SHIM) scores were collected pre-treatment and 3, 6 and 12 months post-implantation. Mixed effect modelling was undertaken to compare baseline, 1-6 month and 7-12 month scores between groups. Poisson regression analysis was performed to correlate dosimetric constraints with acute toxicity. Results: There was no difference between baseline and post-implantation IPSS scores between 6-fraction and 2-fraction groups. SHIM scores for men treated with 6-fractions had a steeper decline at 1-6 months, but resolved at 7-12 months. Pre-treatment alpha-blocker use correlated with worse shortterm acute urinary toxicity. Worsened SHIM score correlated with increasing age, diabetes mellitus and androgen-deprivation therapy. In a dosimetric analysis of outcomes, prostate V150 dose and bladder wall (D01.cc, D1cc, D2cc) dose correlated with increased IPSS score. Conclusion: No increased acute genitourinary or sexual dysfunction has been observed in men when transitioning from 6-fraction to 2-fraction HDR monotherapy. A dosimetric correlation was found between the V150 and bladder wall doses for acute urinary toxicity. Future research should continue to standardize and validate dose constraints for prostate HDR monotherapy patients.