Background: Stereotactic body radiotherapy (SBRT) is increasingly used to treat patients with intermediate-risk prostate cancer (IR-PCa), but there is a lack of early surrogate measures in this patient population treated with SBRT to guide clinicians and patients. We aim to explore the outcomes of IR-PCa patients treated with SBRT and to assess the role of PSA response at 4 years (4yPSARR) as an early surrogate measure given its encouraging results in patients treated with brachytherapy. Methods: Individual patient data from 6 institutions for 820 patients with IR-PCa treated with SBRT between 2006 and 2014 were analyzed. Cumulative incidence of biochemical recurrence (defined by Phoenix criteria) was calculated using Nelson-Aalen estimates, and metastases-free survival and overall survival were calculated using the Kaplan-Meier method. Biochemical recurrence-free survival was analyzed according to 4yPSARR with groups dichotomized based on PSA < 0.4 ng/mL or >0.4 ng/mL and compared using Log-rank test. Results: 820 patients were included, including 549 (67%) with favorable intermediate and 271 (33%) with unfavorable intermediate risk disease defined by NCCN risk group classification. Median age at time of treatment was 70 years. The most common dose, fractionation and treatment schedule was 36.25 Gy in 5 fractions prescribed to the planning target volume delivered every other day. Androgen deprivation therapy was used in combination with SBRT in 9.2% of patients for a median duration of 3 months. Median follow-up was 5.9 years. The cumulative incidence of biochemical recurrence was 7.9% at 5 years. Metastases-free survival and overall survival rates at 5 years were 99.4% and 94.6%, respectively. Median 4yPSARR (n = 504) was 0.2 ng/mL. Biochemical recurrence-free survival in patients with 4yPSARR < 0.4 ng/mL (n = 387) was 99.2%, and in patients with 4yPSARR >0.4 ng/mL (n = 117) was 81.5% at 5 years (p < 0.0001). Conclusions: Prostate SBRT is an effective treatment modality in men with IR-PCa with at least comparable rates of biochemical failure and metastases compared to other standard treatment modalities in patients with IR-PCa. 4yPSARR may represent an early surrogate measure for use in this patient population treated with SBRT and should be included for further study in prospective SBRT trials.