We included severe ED patients (60% diabetic, 85% with cardiovascular disease) that failed to respond to PDE5i therapy, who scored 0-2 on the rigidity scale (RS) during PDE5i therapy.Treatment included 2 sessions/week for 3 weeks, repeated after a 3-week no-treatment interval. At each session LI-ESWT was applied on the penile shaft and crus for 3 minutes in 5 different penile anatomical sites (intensity of 0.09 mj/mm2, 300 shocks/site). One-month after end of treatment the same baseline assessment was repeated. An active PDE5i medication regime was then provided and final erectile function was reassessed. Main endpoints for success were changes in RS and in the International Index of Erectile Function (IIEF-ED) Domain score. We found that LI-ESWT can effectively treat severe ED patients who failed PDE5i therapy. This study further emphasises the physiological effect that LI-ESWT can have on the erectile mechanism.