Objective: To explore safety in adipose-derived regenerative cells (ADRC) therapy, treating erectile dysfunction (ED). Methods: Twenty-one patients with ED after radical prostatectomy, with no signs of recovery using conventional therapy, received a single intracavernous injection of autologous ADRC and were followed for 1 year. Six men were incontinent, and 15 were continent at inclusion. The primary (safety of ADRC therapy) and secondary endpoints (sexual function) were evaluated at 1, 3, 6, and 12 months after ADRC injection by registration of adverse events and validated questionnaires using the international index of erectile function-5 and erection hardness score. Results: No serious adverse events occurred, but 8 reversible minor events related to the liposuction were noted. Eight out of 15 (53%) patients in the continent group reported erectile function sufficient for intercourse at 12 months. Baseline median international index of erectile function-5 scores (6.0; interquartile range [IQR] 3) were unchanged 1 month after the treatment, but significantly increased after 6 to 7 (IQR 17). This effect was sustained at 12 months (median 8; IQR 14). We did not see any improvements in erectile function in the group of incontinent men or among men with ED prior to radical prostatectomy. Conclusion: Intracavernous injection of ADRC is safe in this phase 1 study with a 12-month follow-up.