Purpose: This study aimed to report the early toxicity results of a prospective clinical trial of prostate stereotactic body radiation therapy (SBRT) to the entire prostate with a simultaneous integrated boost (SIB) to magnetic resonance imaging (MRI)-defined focal lesions. Methods and materials: Eligible patients included men with biopsy-proven prostate stage T1c to T2c adenocarcinoma, a Gleason score ≤7, and prostate-specific antigen values of ≤20 ng/mL, who had at least 1 focal lesion visible on MRI and a total prostate volume no greater than 120 cm3. SBRT consisted of a dose of 36.25 Gy to the entire prostate with an SIB of 40 Gy to the MRI-defined lesions, delivered in 5 fractions. The primary purpose of the study was to confirm the feasibility of treatment planning/delivery and to estimate the rate of urinary retention requiring placement of a Foley catheter within 90 days of treatment. This study was to be considered successful if urinary retention occurred in no more than 15% of cases, with a planned enrollment of at least 25 patients. Results: A total of 26 men were enrolled, and all underwent SBRT as planned. Twenty patients (77%) had intermediate-risk features, and the remainder were low risk. A treatment plan that met the protocol-defined goals for all cases was developed. Two patients (7.7%) developed acute urinary symptoms that required the temporary placement of a Foley catheter. No grade 3+ toxicity events were observed. Conclusions: Planning and delivery of prostate SBRT with a whole prostate dose of 36.25 Gy and a focal 40 Gy SIB is feasible. Early follow-up suggests that this treatment is not associated with undue morbidity.