We report on the early toxic effects and quality of life of localized prostate cancer radiation therapy in a randomized trial comparing moderate hypofractionation (MHF) with ultrahypofractionation (UHF). We randomized patients with intermediate- to high-risk localized prostate cancer to radiation therapy with MHF (70 Gy in 28 daily fractions) or UHF (36.25 Gy in 5 weekly fractions). We analyzed early toxic effects (using Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group/Subjective, Objective, Management, Analytic scales) and patient-reported quality of life (using the Expanded Prostate Inventory Composite questionnaire) when all patients had at least 6 months of follow-up. We randomized 80 participants. Two patients withdrew from radiation therapy. We ran analysis on results for 78 patients. The 2 arms were balanced in key patient and disease characteristics, except for a statistically worse baseline urinary function in the UHF arm (International Prostate Symptom Score >7: 68% vs 36%, P=.004). There were no statistically significant differences between the 2 arms in grade 3 or grade 2 toxic effects: grade ≥3 MHF 8%, UHF 2% (P=.235); grade ≥2 MHF 36%, UHF 24% (P=.235). There were also no significant differences in percentages of patients with a "minimal important change" of quality of life in the Incontinence (MHF 36%, UHF 33%; P=.746), Irritative/Obstructive (MHF 56%, UHF 74%; P=.074), or Bowel domains (MHF 58%, UHF 52%; P=.508) on the Expanded Prostate Inventory Composite questionnaire. UHF radiation therapy for prostate cancer is well tolerated, and there were no significant differences in toxic effects and quality of life changes between UHF and MHF up to 6 months after treatment in the current trial.