The treatment options for low-risk prostate cancer (PCa) include active surveillance (AS), external-beam radiation therapy (EBRT), and radical prostatectomy all with 5-year survival rates over 95%. However, each treatment option also carries the risk of negative effects on health-related quality of life (HRQoL). AS has been gaining popularity in recent years, however, data are lacking on its effects on HRQoL. This study aimed to determine whether patients with low-risk PCa, who undergo EBRT, report poorer HRQoL outcomes compared to those managed with AS over a 3-year period. The study population was identified from the Center for Prostate Disease Research Multicenter National Database. Inclusion criteria included a biopsy-confirmed diagnosis of PCa in patients aged 75 years or younger. “Low-risk” PCa was defined using the National Comprehensive Cancer Network criteria: clinical stage T1-T2a, biopsy Gleason score ≤6, and prostate-specific antigen <10 ng/mL. HRQoL data were collected using 2 validated questionnaires: the Expanded Prostate Cancer Index Composite which is designed to evaluate urinary, bowel, sexual, and hormonal function and bother experienced within the past 4 weeks and the 36-item Medical Outcomes Study Short Form (SF-36) survey which measures general, physical and mental health. Of the 499 eligible patients with low-risk PCa, 103 (21%) selected AS and 60 (12%) were treated with EBRT. At baseline, both treatment groups reported comparable HRQoL. EBRT patients experienced significantly worse bowel function and bother at 1 year and 2 years compared to patients managed with AS. Patients who received EBRT were significantly more likely to experience a decrease in more than one functional domain (urinary, sexual, bowel, or hormonal) at 1 year. The limitations of the study include a short follow-up period, small sample size and inability to measure individual physician treatment preferences or recommendations. In addition, 27% of EBRT patients received the therapy at a dose lower than currently recommended dose. Keeping these limitations in mind and that these findings require validation, this study supports the use of AS as a way to preserve HRQoL among low-risk PCa patients.