Purpose <p>The present study aimed to evaluate the midterm efficacy and safety of venous leak embolization in patients with erectile dysfunction (ED) who did not respond to phosphodiesterase-5 inhibitors.</p> Methods <p>From October 2019 to June 2024, ED patients with venous leakage were included from a prospective, multicenter, all-comers, investigator-initiated registry. A mixture of ethiodized oil and modified cyanoacrylate-based glue n-butyl 2 cyanoacrylate monomer (NBCA) was used as liquid embolic agent. Before embolization, venous leak was classified on computed tomography cavernosography. The primary safety outcome measure was any major adverse event up to 12&#xa0;weeks after the procedure. The primary feasibility outcome measure was IIEF-15 (International Index of Erectile Function-15) score improvement ≥ 4 points in ≥ 50% of the subjects at up to 3&#xa0;months, 1&#xa0;year, and annually thereafter.</p> Results <p>One hundred seventy-five consecutive patients with venous leak were included. Successful venous leak embolization was achieved in 193/194 (99.5%) of cases. Nontarget embolization (pulmonary embolisms) occurred in 3/175 (1.7%) patients. The primary feasibility outcome measure at 9.2 ± 11.3&#xa0;months was achieved by 82/138 (59.4%) patients. IIEF-15 scores were 31 ± 22 at baseline, 45 ± 35 up to 3&#xa0;months, and 43 ± 24 at one year. Eighteen of the 175 patients (10.2%) experienced venous leak recurrence (<i>n</i> = 16) or persistence (<i>n</i> = 2) after embolization at 16.1 ± 14.3&#xa0;months.</p> Conclusion <p>Venous leak embolization was effective at midterm follow-up in the majority of patients. Venous leak recurrence is rare due to venous leak recanalization or new collateral vein formation.</p> Graphical Abstract <p></p>