he management of large osseous defects requires innovative intramedullary bone graft harvesting techniques to optimize healing while minimizing complications. Intramedullary bone graft harvesting is, however, associated with potential cardiopulmonary adverse events due to embolic phenomena and systemic inflammation. This study compares the newly introduced aspirator + reaming-aspiration (ARA) concept with the established second-generation Reamer-Irrigator-Aspirator (RIA 2) system, focusing on cardiopulmonary safety in a non-fracture sheep femur model. Sixteen female Merino sheep underwent intramedullary bone grafting using either the RIA 2 system or the ARA concept. The primary outcomes measured were blood loss, hemodynamic parameters, pulmonary function via the Horovitz index, and systemic inflammatory responses postprocedure. Findings revealed minimal and comparable blood loss between the two groups (p = 0.55). Additionally, no significant differences were found in hemodynamic stability (all p ≥ 0.05), pulmonary function (p = 0.96), or systemic inflammation (all p ≥ 0.10) between the RIA 2 system and ARA concept groups, demonstrating the comparable safety profile of the ARA concept to the RIA 2 system. In conclusion, the ARA concept emerges as a viable and effective alternative to the RIA 2 system for intramedullary bone graft harvesting, with similar safety profiles. These promising results advocate for further clinical trials to validate the utility of the ARA concept in human patients.