Background Existing methods for treating erectile dysfunction (ED) do not always provide the necessary therapeutic effect and/or may not be recommended for certain patients. Aim Evaluate the effectiveness of correcting erectile dysfunction using platelet-rich plasma (PRP) and extracorporeal shock wave therapy (ESWT). Material and methods 100 men were randomly assigned to 3 groups. Group 1 (n=20) received ESWT treatment on the penis twice a week for 6 weeks. Group 2 (n=40) and Group 3 (n=40) had two visits per week for 6 weeks, involving both ESWT and PRP injections into the penis. In Group 2, PRP activation was performed using ESWT, while in Group 3, it was done using a 10% solution of CaCl2. Patients were evaluated at 0 and 60 days of the study, assessing IIEF-5, SEP, EHS, GAQ, blood testosterone levels, and penile Doppler ultrasound with PGE1. Results In group 1 IIEF-5 improved from 14.5 (10.5-17) to 19.5 (15.5-21) (?<0.05). SEP changed from 2 (1-2) to 3 (2-4) (?<0.05). EHS improved from 1.5 (1-2) to 3 (2.5-3) (?<0.05). Baseline PSV was 16.3 cm/s (12.2-22.7), at 60 days post ESWT was 24 cm/s (19.4-26.8) (?<0.05) and RI changed from 0.7 (0.7-0.9) to 0.9 (0.8-1) according D-PDU (?<0.05). 14 patients (70 %) noted positive dynamics by GAQ at the last exam. In group 2 IIEF-5 was 13 (11-15) at 0 days, 18 (16-20) at 60 day (?<0.05). SEP improved from 2 (1.5-2) to 3 (3-4) (?<0.05). EHS changed from 2 (1-2) to 3 (2-3) (?<0.05). D-PDU results demonstrated increase median PSV 15.6 cm/s (12.1-22.8) to 27 cm/s (20.6-33.5) (?<0.05) and median RI from 0.8 (0.7-1) to 1 (0.8-1) (?=0.02). 34 men declared positive effects according to GAQ (85 %) In group 3 IIEF-5 results improved from 13 (9-15) to 18.5 (15-20.5) (?<0.05). SEP improved from 2 (1-2) to 3 (3-4) (?<0.05). EHS changed from 1 (1-2) to 3 (3-3) (?<0.05). PSV increased from 17 cm/s (10.3-25) to 27.8 cm/s (20-36.6) (?<0.05). RI improved from 0.8 (0.7-0.9) to 0.9 (0.8-1) (?=0.005). 33 patients respond to an improvement of erectile functions (82.5 %) by GAQ. Conclusion All treatment methods were well-tolerated by all patients. The study results indicate a positive trend in improving erectile function and increasing total testosterone levels in the blood. When comparing groups, combination therapy significantly improves erectile function according to SEP, EHS, and penile Doppler ultrasound assessments. ESWT can be suggested as an activator for PRP. © 2024 ABV-press Publishing House. All rights reserved.