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BACKGROUND Vascular-targeted photodynamic therapy (VTP) is an approved treatment option for unilateral low-risk prostate cancer (PCa). OBJECTIVE Herein, we report our initial experience of patients treated by VTP. We compared short-term functional and oncological outcomes with those of a consecutive cohort of patients undergoing radical prostatectomy (RP) for unilateral low-risk PCa. DESIGN, SETTING, AND PARTICIPANTS Patients with unilateral low-risk PCa undergoing VTP (n = 41) and RP (n = 49) were evaluated in a real-world setting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Oncological outcome after VTP was measured by magnetic resonance imaging-based rebiopsy at 12 and 24 mo. Functional outcome after 1 yr was investigated by International Index of Erectile Function 5 and International Prostate Symptom Score questionnaires. Continence was evaluated by pad use. RESULTS AND LIMITATIONS In 12- and 24-mo control biopsy (n = 22) after VTP, 45% of VTP patients showed no evidence of PCa. Both low- and intermediate-risk PCa were detected in 27% of patients. None of the RP patients had a PCa recurrence. Of VTP and RP patients, 71% and 30%, respectively, preserved erectile function. Of VTP patients, 88% had no bladder outlet obstruction. Of RP patients, 96% and 4% used zero to one and two or more pads per day, respectively. Data acquisition was performed outside of a clinical trial. The short-term follow-up and the small number of rebiopsied patients have to be considered. CONCLUSIONS VTP is a promising treatment option in unilateral low-risk PCa presenting a lower complication profile than RP in a real-world setting. However, recurrence and progression after VTP are common in this low-risk PCa cohort, and have to be discussed critically with patients who wish VTP instead of active surveillance. Therefore, a rigorous surveillance strategy with multiparametric magnetic resonance imaging and control biopsy is required. PATIENT SUMMARY Vascular-targeted photodynamic therapy (VTP) is a promising therapy option in patients with unilateral low-risk prostate cancer. However, tumour recurrence has to be taken into account. Noninferiority of VTP to standard curative treatment options still has to be confirmed.