Background To explore if early perfusion-weighted magnetic resonance imaging (PWI) may be a promising imaging biomarker to predict local recurrence (LR) of brain metastases after stereotactic radiosurgery (SRS). Methods This is a prospective pilot study of adult brain metastasis patients who were treated with SRS and imaged with PWI before and 1 week later. Relative cerebral blood volume (rCBV) parameter maps were calculated by normalizing to the mean value of the contralateral white matter on PWI. Cox regression was conducted to explore factors associated with time to LR, with Bonferroni adjusted p<0.0006 for multiple testing correction. LR rates were estimated with the Kaplan-Meier method and compared using the log-rank test. Results Twenty-three patients were enrolled from 2013 through 2016, with 22 evaluable lesions from 16 patients. After a median follow-up of 13.1 months (range: 3.0–53.7), 5 lesions (21%) developed LR after a median of 3.4 months (range: 2.3–5.7). On univariable analysis, larger tumor volume (HR 1.48, 95% CI 1.02–2.15, p = 0.04), lower SRS dose (HR 0.45, 95% CI 0.21–0.97, p = 0.04), and higher rCBV at week 1 (HR 1.07, 95% CI 1.003–1.14, p = 0.04) had borderline association with shorter time to LR. Tumors >2.0cm3 had significantly higher LR than if <2.0cm3: 54% vs 0% at 1 year, respectively, p = 0.008. A future study to confirm the association of early PWI and LR of the high-risk cohort of lesions >2.0cm3 is estimated to require 258 patients. Conclusions PWI at week 1 after SRS may have borderline association with LR. Tumors <2.0cm3 have low risk of LR after SRS and may be low-yield for predictive biomarker studies. Information regarding sample size and potential challenges for future imaging biomarker studies may be gleaned from this pilot study.