Premature ejaculation is a sexual debilitating condition affecting a large number of men worldwide and leading to important dysfunctions influencing the patients' affective and emotional life. Hyaluronic acid is a natural and safe compound that has been widely used not only in the aesthetic medicine clinic, but also for treatment of osteoarthritis. The present study shows the effectiveness of a hyaluronic acid-based procedure for treatment of premature ejaculation. A hundred and ten male patients were treated with hyaluronic acid injections in the deep dermis of their glans penis to increase the volume and the circumference of their penis to prevent male premature ejaculation and improve the patients' and their partners' sexual satisfaction. The intravaginal ejaculation latency time increased significantly from a baseline value of 88.34±3.14 s to 293.14±8.16 s after 6 months from the procedure. Maximal glandular circumference increased from 98.51±0.71 mm to 114.35±0.66 mm after 6 months from the procedure. At 6-month follow-up, patients' self-rated satisfaction was 5.3±0.07 (range: 4-6). At the follow-up, partners' self-rated satisfaction was 5.1±0.09 (range: 3-6). The present clinical study showed that hyaluronic acid injection is a promising treatment for premature ejaculation. The effect of the procedure in the long-term follow-up needs to be clarified.