Background: Salvage radiation therapy is a recognized management option for patients who develop biochemical failure following radical prostatectomy. However, given the documented long natural history of biochemically relapsed prostate cancer after prostatectomy, questions remain on the value of early salvage intervention vs initial expectant management, especially with regards to more critical clinical rather than biochemical endpoints. We sought to determine the impact of early salvage radiotherapy (initiated at PSA 0.2 - 0.5 ng/ml) on metastasis-free survival in patients who receive salvage radiotherapy following prostatectomy for clinically localized prostate cancer. Methods: Using tumor registry data, we identified 408 patients who received salvage radiation therapy between 1986 – 2016 at our institution. We analyzed association between survival outcomes and prognostic factors, including pre-treatment and nadir prostate-specific antigen (PSA), interval between prostatectomy and initiation of salvage RT, use of neoadjuvant/concurrent hormonal suppression, and adverse pathologic features, including Gleason score, extraprostatic extension, seminal vesicle invasion, nodal involvement, and margin status. Univariate analyses and multivariable-adjusted Cox proportional hazards models were constructed to assess association between these clinical and pathologic features and duration of biochemical relapse-free survival (bRFS) and metastasis-free survival (MFS). Construction of Kaplan-Meier survival curves stratifies survival by predictive features. Results: Overall, 187 (45.8%) patients received salvage radiotherapy while PSA levels were 0.2 - 0.5 ng/ml (early salvage). One hundred thirty three (32.6%) patients received neoadjuvant/concurrent androgen deprivation therapy (ADT). Median radiation dose was 68.4 Gy and did not differ significantly between treatment subgroups. Independent of pathologic features and use of ADT, early-salvage at lower PSA levels was the most significant predictor of improved bRFS and MFS, HR = 0.52 (95% CI [0.35, 0.79], p = 0.002), and HR = 0.58 (95% CI [0.37, 0.91], p = 0.02), respectively. Seminal vesicle invasion was associated with shorter interval to biochemical failure (HR = 1.79 (95% CI [1.07, 2.98], p = 0.03), but not significant difference in MFS. Conversely, nodal involvement was a significant predictor of worse MFS, with HR = 2.18 (95% CI [1.04, 4.57], p = 0.04). Notably, interval between prostatectomy and initiation of salvage radiation was not a significant prognostic factor for bRFS or MFS. Conclusions: Independent of pathologic features and use of ADT, the initiation of salvage radiation therapy early after biochemical relapse (PSA ≤ 0.5 ng/ml) following prostatectomy is associated with increased metastasis-free as well as biochemical relapse-free survival.