The present study aimed to analyze the effect of predisposing clinical factors for severe erectile dysfunction (ED) in patients treated with focal therapy using high-intensity focused ultrasound (HIFU) for localized prostate cancer (PC). Patients without severe ED (International Index of Erectile Function-5 [IIEF-5] score ≥ 8) before focal HIFU therapy were included. A total of 92 of the 240 patients met the inclusion criteria and were included. The rate of severe ED (IIEF-5 ≤ 7) was 36% 12 months after treatment. Multivariable logistic regression analysis showed that the pre-procedural lower IIEF-5 score (odds ratio [OR] 0.812, p = 0.005), the pre-procedural lower score of the sexual domain of the Expanded Prostate Cancer Index Composite (OR 0.960, p = 0.038), and the treatment of the edge of the peripheral zone (PZ) in proximity to the neurovascular bundle (NVB) [treated vs. untreated, OR 8.048, p = 0.028] were significant risk factors for severe ED at 12 months after treatment. In conclusion, pre-procedural lower erectile function and treatment of the part in proximity to the NVB were significant risk factors for severe ED after focal therapy.