Background: Partial gland ablation (PGA) for MRI-invisible prostate cancer (PCa) remains controversial, and we compared treatment failure rates, adverse events, and health-related quality-of-life outcomes (HRQoL) following PGA in subjects with MRI-visible vs. MRI-invisible lesions. Methods: Retrospective review was done of primary PGA therapy (cryoablation, irreversible electroporation, and high-intensity focused ultrasound) performed between January 2017 and 2022 at Weill Cornell Medical Center. Analysis was restricted to men with at least one post-PGA prostate biopsy. Men with PCa on systematic biopsy outside of the MRI-targeted zone were categorized as having MRI-invisible lesions. Failure of PGA was defined as persistence or recurrence of Gleason grade group (GGG) ≥2 on surveillance biopsy for subjects diagnosed with GGG ≥2 PCa. For patients treated for GGG 1 PCa, failure was defined by the detection of GGG ≥1 PCa. Adverse events were captured by the Clavien-Dindo classification and HRQoL outcomes were captured by the Expanded Prostate Cancer Index-Clinical Practice (EPIC-CP). Groups were compared using Pearson’s chi-squared test and the 2-sided Wilcoxon-Mann-Whitney test. Results: Out of 115 men were treated for primary prostate cancer, 89 men had at least one surveillance biopsy performed, and 87 men had available pre-treatment MRI data. Out 79 subjects treated with MRI-visible lesions and 34 subjects treated with MRI-invisible lesions, 59 and 28 subjects, respectively, had surveillance biopsy data. Median (IQR) follow-up was 15.5 months (7.7-25.5) in the overall cohort; median follow-up was not significantly different between the MRI-visible and MRI-invisible groups (15 vs. 15 months, p-value=0.766). Failure of PGA occurred in 43 (48.3%) of total subjects. Failure of PGA was not significantly different between the MRI-visible and MRI-invisible groups (50.9% vs. 42.9%, p-value=0.502). Mean total EPIC-CP scores were not significantly different between both groups at baseline, 3, 6, and 12 months after PGA. Additionally, rates of 30-day complications were not significantly different between both groups. Conclusions: Failure is evident in almost half of patients treated with PGA therapy. Oncologic and functional treatment outcomes after focal therapy are similar between patients with MRI-visible and MRI-invisible lesions.