ObjectiveTo assess histopathological outcomes, as well as feasibility and safety of targeted microwave ablation (TMA) via the Trinity® system (KOELIS, La Tronche, France).Patients and methodsProspective, single‐institution, interventional Phase IIa study with an ‘ablate‐and‐resect’ design. In all, 11 patients diagnosed with localised prostate cancer (PCa) underwent TMA via the Trinity system under conscious sedation in an outpatient setting using a single transrectal TATO® 18‐G antenna with different treatment regimens. Magnetic resonance imaging (MRI) and robot‐assisted radical prostatectomy (RARP) were conducted at 7 days and 1 month after TMA, respectively. Nine patients received RARP, and two patients chose to withdraw their consent following TMA. These men chose an active surveillance protocol upon confirmation of a low‐risk prostate cancer diagnosis. Functional outcomes and adverse events were evaluated at baseline and follow‐up visits using validated questionnaires. Prostate volumetry and confirmation of necrosis were carried out through MRI and whole‐mount histopathological examination.ResultsThe TMA was successfully executed, and all patients were discharged on the same day. No severe adverse events (Common Terminology Criteria for Adverse Events Grade ≥3) were reported at the 7‐day and 1‐month follow‐up visits. Additionally, no declines were observed in urinary, sexual and ejaculation functional outcomes. T1‐weighted MRI revealed clear and well‐defined ablation zones. The RARP was executed without difficulty, particularly during the dissection of the posterior plane. As a result, no intraoperative complications were encountered. Histopathological assessment on surgical specimens confirmed the absence of viable cells, indicating complete necrosis of the ablative zone if a power intensity >10 W was used during TMA. Ablation zone volumetry revealed no notable distinctions between the three‐dimensional segmentation of the virtual ablation zone at TMA (median volume: 2 mL) and MRI (median volume: 1.923 mL). Conversely, a significant reduction was noted in the surgical specimen (median volume: 0.221 mL).ConclusionsTargeted microwave ablation via the Trinity system for localised PCa treatment proves to be a secure and feasible procedure, with complete necrosis evidence within the ablation zone on surgical specimens.