Background: There is growing evidence for the use of High Dose Rate (HDR) brachytherapy as monotherapy for the treatment of low and intermediate risk prostate cancer patients. With the increasing availability of magnetic resonance imaging (MRI) there is an opportunity to further escalate dose to the dominant intraprostatic lesion (DIL). We report acute toxicity of this prospective phase I/II trial. Methods: Eligible patients had low- and intermediate risk prostate cancer, IPSS < 16, were medically eligible for HDR brachytherapy treatment and had an identified DIL on multiparametric MRI (mpMRI) prior to brachytherapy treatment. Patients were treated with 19 Gy delivered in one fraction to the whole prostate. A 0-5mm expansion was applied to the DIL to define the PTV DIL, with a DIL PTV D90 to receive > 23Gy based on previous experience. Toxicity was assessed using CTCAE v.4.0 at baseline, 6 weeks 3, 6, 9 and 12 months post brachytherapy. Results: A total of 34 patients have undergone HDR monotherapy treatment with an integrated DIL boost with a median follow up of 6 months. The median age was 67 years (range 46-80). At presentation, median PSA was 6.1 ng/mL (range 2.5-16.4). Three, 26, and 6 patients had low, low intermediate and high intermediate risk disease. Baseline characteristics were PIRAD 5 (n = 21) and PIRAD 4 (n = 13), median prostate volume was 38 cc (range 18-54). The median DIL volume was 2.8 cc (range 1.14-7.8). The median DIL D90 was 27 Gy (range 19-35.8). No patients experienced acute or late grade 2+ GI toxicity. The percentage of acute grade 2 GU toxicity were as follows; retention 62%, frequency 18%, urinary tract pain 6%. One patient had acute clot retention requiring catheterization x1 day and has been catheter-free since. Late grade 2 GU toxicity (alpha blockers) was reported in 6/16 patients at 6 months. Conclusions: The use of mpMRI to define and further escalate dose to the DIL using HDR monotherapy is feasible with minimal acute toxicities. Further long term follow up is required to determine the efficacy of treatment, and impact on quality of life and late toxicities. Clinical trial information: NCT02623933