Abstract Several trials focusing on focal laser ablation (FLA) for patients diagnosed with localized prostate cancer reported encouraging short-term outcomes. However, those studies also demonstrated the necessity of further trials; in particular, to determine mid-term and long-term oncologic outcomes. Our study suggested that FLA had a higher risk of all-cause mortality but an insignificantly lower risk of cancer-specific mortality compared with radical prostatectomy, which certainly requires more high-quality trials to confirm. To our knowledge, we are the first to report the mid-term survival outcomes of FLA treating localized prostate cancer. Background: Focal therapy for localized prostate cancer (PCa) remains investigational. We aimed to investigate the oncologic outcomes of focal laser ablation (FLA) and compare them with those of radical prostatectomy (RP). Patients and Methods: Patients treated with FLA or RP for localized PCa between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier curves and multivariate Cox proportional hazard models were utilized to calculate the survival benefits. Propensity score (PS) matching and adjusted standardized mortality ratio weighting (SMRW) models were used to balance the 2 groups. Subgroup analyses according to tumor stage, prostate-specific antigen level, and Gleason score were also conducted. Results: A total of 12,875 patients were included, of whom 12,433 were treated with RP, whereas 442 were treated with FLA; 321 pairs of patients were eventually matched. Baseline characteristics were well-balanced by PS matching. The mean follow-up was 59.62 months for the RP group and 62.26 months for the FLA group. Before matching, the FLA group had lower but statistically insignificant cancer-specific mortality (CSM) (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.15-2.45; P ?.4879) and higher any-cause mortality (ACM) (HR, 2.35; 95% CI, 1.38-3.98; P ?.0016) compared with the RP group, which was supported by the outcomes in the PS-matched cohort (CSM: HR, 0.82; 95% CI, 0.18-3.67; P ?.7936; ACM: HR, 2.35; 95% CI, 1.38-3.98; P ?.0016) and the SMRW model (CSM: HR, 0.61; 95% CI, 0.15-2.44; P ?.4877; ACM: HR, 2.01; 95% CI, 1.18-3.42; P ?.0103). Conclusion: Our study suggests that FLA had a higher risk of ACM but an insignificantly lower risk of CSM compared with RP. More high-quality trials are needed to confirm and expand our findings.