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PURPOSE To present the clinical commissioning of a novel 103Pd directional brachytherapy device (CivaSheet™) for intraoperative radiation therapy. METHODS AND MATERIALS Clinical commissioning for the CivaSheet™ consisted of establishing: (i) source strength calibration capabilities, (ii) experimental verification of TG-43 dosimetry parameters, (iii) treatment planning system validation, and (iv) departmental practice for dose specification and source ordering. Experimental verification was performed in water with radiochromic film calibrated with a 37kVp x-ray beam. Percentage difference ([measurements – calculation] / calculation) and distance to agreement (difference between film-to-source distance and distance that minimized the percentage difference) were calculated. Nomogram values (in U/100 Gy) for all configuration (up to 20 × 20 sheets) were calculated for seed ordering. Clinical commissioning was used on patients enrolled in an ongoing IRB-approved protocol. Results A source calibration procedure was established and the treatment planning system was commissioned within standard clinical uncertainties. Percentage dose differences (distances to agreement) between measured and calculated doses were 8.6% (−0.12mm), 0.6% (−0.01mm), −6.4% (0.22mm), and −15.8% (0.72mm) at depths of 2.3mm, 5.1mm, 8.0mm, and 11.1mm respectively. All differences were within the experimental uncertainties. Nomogram values depended on sheet size and spatial extent. A value of 2.4U/100 Gy per CivaDot™ was found to satisfy most cases, ranging from 2.3 to 3.3U/100 Gy. Nomogram results depended on elongation of the treatment area with a higher variation observed for smaller treatment areas. Post-implantation dose evaluation was feasible. CONCLUSIONS Commissioning and clinical deployment of CivaSheet™ was feasible using BrachyVision™ for post-operative dose evaluation. Experimental verification confirmed that the available TG-43 dosimetry parameters are accurate for clinical use.