<b><i>Introduction:</i></b> Diffusion-weighted imaging (DWI) as part of multiparametric magnetic resonance imaging (mpMRI) is an important sequence for the detection of prostate cancer (PCa). The objective of this retrospective analysis was to evaluate changes in apparent diffusion coefficient (ADC) measurements in biopsy-proven PCa undergoing TULSA-PRO (MR-guided transurethral ultrasound ablation of the prostate) at 3.0 T after 1, 3, and 6–12 months posttreatment. <b><i>Methods:</i></b> Nineteen patients underwent follow-up examinations after 1, 3, and 6–12 months including mpMRI at 3.0 T and urological-clinical examinations with quantitative analysis of ADCs. <b><i>Results:</i></b> In PCa, a significant increase of ADC values after 6–12 months was measured after TULSA-PRO treatment by 29.1% (pre-TULSA: 0.79 ± 0.16 × 10⁻³ mm²/s, 6–12 months: 1.02 ± 0.35 × 10⁻³ mm²/s), while the corresponding value in the reference tissue decreased by 48.5% (pre-TULSA: 1.20 ± 0.15 × 10⁻³ mm²/s, 6–12 months: 0.91 ± 0.29 × 10⁻³ mm²/s). The mean ADC values in the early follow-up groups at 1 and 3 months did not change significantly. <b><i>Conclusion:</i></b> DWI with ADC as part of mpMRI can serve as a biomarker to dynamically monitor the follow-up after TULSA after 6–12 months. For early posttreatment progression, it is not suitable due to too many confounding variables.