We sought to determine whether the use of the Reamer-Irrigator-Aspirator (RIA) device resulted in a decreased amount of fat emboli compared with standard reaming (SR) when performing intramedullary (IM) nailing of femoral shaft fractures. Prospective randomized clinical trial. Multi-centered trial, level I trauma centers. All eligible patients who presented to participating institutions with an isolated femoral shaft fracture amenable to fixation with antegrade IM nailing. Thirty-one patients were enrolled: nine were excluded because of technical difficulties with the transesophageal echocardiogram (TEE) recording. Therefore, the study comprised 22 patients: 11 patients randomized to the SR group and eleven patients randomized to the RIA group. Antegrade IM nailing of a femoral shaft fracture with standard reamers or the RIA device. All patients were monitored intraoperatively with a continuous TEE to assess embolic events in the right atrium. A radial arterial line was used to monitor blood gases and potential systemic effects of emboli. Duration, size, and severity of emboli as measured by TEE. The operative procedure was divided into 6 distinct stages: preoperative, reduction, guidewire passage, reaming, nail insertion, and postoperative. There was no significant difference in emboli between the RIA and SR groups preoperatively, during fracture reduction, guidewire insertion, or postoperatively. Measured with a standardized scoring system, there was a modest reduction in total emboli score in the RIA group during reaming (SR 5.30 [SD; 1.81] vs. RIA 4.05 [SD; 2.19], P = 0.005) and during nail insertion (SR 5.09 [SD; 1.74] vs. RIA 4.25 [SD; 1.89], P = 0.03). We were unable to correlate this reduction with any improvement in physiologic parameters (mean arterial pressure, end-tidal CO2, O2 saturation, pH, paO2, and paCO2). This study showed a modest reduction of embolic debris during the reaming and nail insertion segments of the operative procedure. We were unable to correlate this with any change in physiologic parameters. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.