Background: The purpose of this study is to examine the combination of the mechanical effects of penile therapy with vacuum erection devices (VEDs) plus PDE5i, which improve clinical outcomes after extracorporeal shockwave therapy (ESWT) in men affected by erectile dysfunction (ED) associated with Peyronie’s disease (PD). Methods: A total of 153 medical records of patients affected by PD in stable stage with ED and treated with ESWT were divided into two groups. Group A (GA) included 72 men treated with ESWT, mechanical stretching with VEDs and PDE5ì (Tadalafil 5 mg), and Group B (GB) included 81 men who received only ESWT plus Tadalafil 5 mg with the same protocol of GA. The patients in both groups were assessed at baseline and follow-up for erectile function, painful erections, penile plaque size, and penile curvature. The results were evaluated at baseline and 3, 6, and 12 months after the treatments. Results: Three months after the treatment, GA patients had a reduction in penile curvature degree from a mean ± SD of 33.91 ± 8.34° at baseline to a mean ± SD of 19.46 ± 7.15° after 12 months, whereas pain in an erection or during intercourse was resolved completely in 88.9% of the patients. The mean ± SD IIEF-15 score of patients affected by severe/moderate ED further improved significantly in the GA group (p < 0.001) after 3, 6, and 12 months of treatment. There were no permanent adverse sequelae after treatments. Conclusions: The regular use of a VED plus Tadalafil in patients who had undergone ESWT significantly provided more benefit in patients with PD in terms of penile deformity, pain, and erectile function.