Importance: Patients diagnosed with localized prostate cancer have to decide among treatment strategies that may differ in their likelihood of adverse effects. Objective: To compare quality of life (QOL) after radical prostatectomy, external beam radiotherapy and brachytherapy vs. active surveillance. Design/Setting/Participants: Population-based prospective cohort of 1,141 men with newly-diagnosed prostate cancer were enrolled from January 2011 through June 2013 in collaboration with the North Carolina Central Cancer Registry (Rapid Case Ascertainment). 57% of eligible men enrolled. Median time from diagnosis to enrollment was 5 weeks, and all men were enrolled with written informed consent prior to treatment. Final follow-up date for current analysis was September 9, 2015. Exposure: Treatment – radical prostatectomy, external beam radiotherapy, brachytherapy, or active surveillance. Main Outcomes and Measures: Quality of life using the validated instrument Prostate Cancer Symptom Indices was assessed at baseline (pre-treatment), and 3, 12, 24 months after treatment. The instrument contains 4 domains – sexual dysfunction, urinary obstruction and irritation, urinary incontinence, and bowel problems – each scored from 0 (no dysfunction) to 100 (maximum dysfunction). Propensity-weighted mean domain scores were compared between each treatment group vs. active surveillance at each time point. Results: 314 men pursued active surveillance (27.5%), 249 external beam radiotherapy (21.8%), 109 brachytherapy (9.6%), and 469 radical prostatectomy (41.1%). After propensity weighting, median age was 66-67 years across groups, and 77-80% were white. Propensity-weighted baseline sexual dysfunction scores were 41.8-46.4 across groups, urinary obstruction and irritation 20.8-22.8, urinary incontinence 9.7-10.5, and bowel problems 5.7-6.1. Compared to active surveillance, mean sexual dysfunction scores worsened by 3 months for radical prostatectomy (+36.2 points, 95% CI 30.4-42.0), external beam radiotherapy (+13.9, 95% CI 6.7-21.2) and brachytherapy (+17.1, 95% CI 7.8-26.6) patients. Brachytherapy (+20.5 vs. active surveillance, 95% CI 15.1-25.9) and external beam radiotherapy (+11.7, 95% CI 8.7-14.8) were associated with acute worsening of urinary obstruction and irritation, radical prostatectomy (+33.6, 95% CI 27.8-39.2) with urinary incontinence, and external beam radiotherapy (+4.9, 95% CI 2.4-7.4) bowel symptoms. By 24 months, mean scores between treatment groups vs. active surveillance were not significantly different in most domains. Conclusions and Relevance: In this cohort of men with localized prostate cancer, each treatment strategy was associated with distinct patterns of adverse effects over 2 years. These findings should be used to promote treatment decisions that incorporate individual preferences.