PURPOSE/OBJECTIVE(S): Stereotactic Body Radiation Therapy (SBRT) is increasingly utilized as a definitive treatment option for patients with prostate adenocarcinoma, especially in the low or intermediate risk setting. The aim of this study is to assess the late toxicity and biochemical recurrence rates of a single institution prospective clinical trial evaluating prostate SBRT with simultaneous integrated boost (SIB) targeting focal lesions as defined by magnetic resonance imaging (MRI). MATERIALS/METHODS: Patients were eligible if they had biopsy-proven low or intermediate risk prostate adenocarcinoma with initial prostate specific antigen (PSA) values ≤20 ng/mL, clinical stage from T1c to T2c, and Gleason score ≤7. Patients also had to have one or more focal lesions on MRI and an MRI-defined total prostate volume of < 120 cm3. All patients received SBRT delivered to the entire prostate to a dose of 36.25 Gy in 5 fractions with an SIB to the lesions seen on MRI to 40 Gy in 5 fractions. Late toxicity was defined as any possible treatment-related adverse event occurring after three months from the completion of SBRT and graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Biochemical recurrence was defined by the Phoenix definition of PSA increase of 2 ng/mL above the nadir. RESULTS: A total of 26 patients were enrolled, and all enrolled patients underwent planned SBRT. Six patients (23.1%) had low risk disease and twenty patients had intermediate risk disease (76.9%). Eight patients (30.8%) received androgen deprivation therapy. Median follow up was 40.5 months (range 12-64 months). No biochemical failures have yet been observed. Three patients (11.5%) experienced late grade 2 genitourinary (GU) toxicity requiring cystoscopy; two of these three patients experienced hematuria requiring cystoscopy and one patient experienced dysuria requiring cystoscopy. Six patients (23.1%) had late grade 2 GU toxicity requiring medications such as tamsulosin or oxybutynin. Two patients (7.7%) had late grade 2 gastrointestinal (GI) toxicity; both patients experienced hematochezia requiring colonoscopy and were found to have proctitis requiring steroids per rectum. There was no grade 3 or higher toxicity events observed. CONCLUSION: The results of this study support that SBRT to the entire prostate to a dose of 36.25 Gy in 5 fractions with focal SIB to 40 Gy in 5 fractions is not associated with undue late GI or GU toxicity. Thus far, this regimen has excellent biochemical control. Focal dose escalation with an SIB planning approach may be an opportunity to improve biochemical control while limiting dose to nearby organs at risk.