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Background: Erectile dysfunction (ED) affects men’s life desperately and the incidence increases continuously. There are a few lines of ED therapy, but there are still many ED cases that have not treated utterly. Therefore, research is needed to obtain the most appropriate line of ED therapy, based on the underlying mechanism of ED. The aim of this study is to analyze the effect of oral daily 2.5 mg of tadalafil administration and twice weekly Low Intensity Extracorporeal Shockwave Therapy (Li-ESWT) for 4 weeks in erectile dysfunction patients, based on Peak Systolic Velocity (PSV) and Vascular Endothelial Growth Factor (VEGF). Methods: A 26-sample clinical trial was conducted with pre and post-test control group design. Random allocation was done to divide the samples into two groups. Control group was given 2.5 mg oral daily tadalafil, while the experimental group, additional twice weekly Li-ESWT was given. Therapies were given for 4 weeks. All subjects were assessed using Erection Hardness Score (EHS) score, International Index of Erectile Function (IIEF-5) score, and Color Doppler Ultrasonography (CDUS) penis for PSV, and plasma level of VEGF twice, prior to and after therapy. Results: The experimental group showed significant improvement compared to the control group in EHS (delta) 2 (1–2) vs 1 (0–2); IIEF-5 (delta) 7 (3–15) vs 4 (0–11); PSV (delta) 2.60 ± 1.34 vs 1.28 ± 1.86; and VEGF (delta) 26.69 ± 24.23 vs 6.32 ± 25.43. Conclusions: Li-ESWT and tadalafil combination therapy improved erectile dysfunction, specifically based on PSV and VEGF parameters.