Purpose Magnetic resonance imaging guided focal laser ablation is an investigational strategy for the treatment of prostate cancer. Materials and Methods This phase II evaluation of focal laser ablation included men with stage T1c-T2a, prostate specific antigen less than 15 ng/ml or prostate specific antigen density less than 0.15 ng/ml3 , Gleason 7 or less in 25% or less of biopsies and magnetic resonance imaging with 1 or 2 lesions concordant with biopsy detected cancer. At 3 months all patients underwent magnetic resonance imaging with biopsy of ablation zone(s). At 12 months all underwent magnetic resonance imaging and systematic biopsy. I-PSS (International Prostate Symptom Score) and SHIM (Sexual Health Inventory for Men) scores were collected before focal laser ablation, and at 1, 3 and 12 months. The primary end point was no cancer on the 3-month ablation zone biopsy. Secondary end points were safety, 12-month biopsy, and urinary and sexual function. Results In the 27 men median age was 62 years and mean prostate specific antigen was 4.4 ng/ml. Biopsy Gleason score was 6 in 23 patients (85%) and Gleason 7 in 4 (15%). Seven men (26%) had low volume Gleason 6 disease outside the intended ablation zone(s). At 3 months 26 patients (96%) had no evidence of cancer on magnetic resonance imaging guided biopsy of the ablation zone. No significant I-PSS changes were observed (each p >0.05). SHIM was lower at 1 month (p = 0.03), marginally lower at 3 months (p = 0.05) and without a significant difference at 12 months (p = 0.38). At 12-month biopsy cancer was identified in 10 patients (37%), including in the ablation zone(s) in 3 (11%) and outside the ablation zone(s) in 8 (30%) with cancer in and outside the ablation zone in 1. Conclusions In select men with localized prostate cancer and visible magnetic resonance imaging lesions focal laser ablation has an acceptable morbidity profile and is associated with encouraging short-term oncologic outcomes. Significantly longer followup is mandatory to fully assess this novel treatment.