Renal disease is epidemic in the United States with approximately 8 × 106 people having chronic kidney disease. Renal biopsies are widely used to provide essential diagnostic information to physicians. However, the risk of bleeding complications possibly leading to life-threatening situations results in the contra-indication of biopsy in certain patient populations. Safer renal biopsies will allow more accurate diagnosis and better management of this epidemic health problem. We report the preclinical testing of a novel biopsy device called the therapeutic injection system (TIS). The device introduces a third stage to the standard two-stage side-cut percutaneous biopsy process. The third stage is designed to reduce bleeding complications by injecting a hemostatic plug at the time of biopsy. Laboratory evaluation and preliminary in vivo animal testing using an anticoagulated porcine model of the TIS and Bard Monopty® (Bard Medical, Covington, GA) control device were performed. The hemostatic material Gelfoam® (Pfizer, Brussels, Belgium) was selected as the active material comprising the hemostatic plugs. The performance of two composite plugs, one composed of polyvinyl alcohol (PVA) combined in 2:1 and 12:1 ratios with the hemostatic material, and one plug composed of 100 hemostatic material were tested. Stroke sequence and hemostatic plug deployment were verified by sequential firing of the TIS biopsy needle into clear gelatin and ex vivo bovine kidney specimens. In vivo trials with porcine specimens revealed a significant reduction in blood loss (8.1 3.9 ml, control versus 1.9 1.6 ml, 12:1 PVA/hemostatic, TIS, = 0.01, = 6). The 100 hemostatic plug showed a substantial and immediate reduction in blood loss (9.2 ml, control versus 0.0 ml, TIS, = 1). The prototype device was shown to work repeatedly and reliably in laboratory trials. Initial results show promise in this approach to control post biopsy bleeding. This solution maintains the simplicity and directness of the percutaneous approach, while not significantly changing the standard percutaneous biopsy procedure.