Background: Former studies showed a time-dependent worsening of sexual or urinary long term side effects following surgery or radiotherapy that affected prostate cancer (PCa) patients’ health-related quality of life (HRQoL) though it was not possible to discriminate between age- and treatment-related symptoms. We sought to compare HRQoL and urological dysfunction at 3 years between PCa patients and general population based on the data from the EPICAP population-based case-control study. Methods: Eligible cases were men < 75 years old, diagnosed with PCa between 2012 and 2014. Controls were recruited in the general population and paired on age. Questionnaires were given to the patients at 3 years after intervention. Primary objective was to compare HRQoL using the EORTC QLQ-C30 questionnaire at 3 years between patients and the general population. Secondary objective was to perform the same comparison for the impact of diagnosis or/and treatments on urinary (IPSS, ICS) or sexual dysfunctions (IEEF-5), anxiety (HADS), and occupational integration. Results: 376 eligible patients had sent back their questionnaires and 188 controls were paired on age (ratio 2:1). Treatments were: RP (radical prostatectomy) (187), RT (radiation therapy) or HIFU (High-intensity Focused Ultrasound) (54), combination of treatment (CT) (90) and watchful waiting (WW) (39) at the time of the study. There was no difference in global health status dimension between patients and controls (p = 0.19). Patients had worse social functioning than controls (24.3% vs 16.3%, p = 0.0209) and cognitive function score was worse in CT versus WW patients (p = 0.039). Significant differences in erectile dysfunction (IIEF6) were observed depending on treatment (81% for RP vs 65% for RT vs 72% for CT vs 33% for WW, p < 0.0001). Conclusions: Despite similar global health status dimension score at 3 years after diagnosis between patients and controls, analyzes of the EPICAP study showed differences in PCa sequelae and emphasize the balance between benefit and risk of PSA testing. This is the first study evaluating the different types of sequelae as a function of treatments.