Abstract Effective reflection distance (ERD), a conceptual distance to a major reflection site from the aortic root, is associated with aging and pressure augmentation index (AIx) in clinical population. However, it is poorly understood how ERD varies and associates with AIx within a subject when the hemodynamic condition is changed extensively by acute pharmacological interventions. Methods In 13 anesthetized dogs, we measured aortic pressure (AP) and flow (AF) and femoral arterial flow (FF). Using AP, AF and FF, ERD based on an arterial model comprising a tube with frequency-dependent load (ERD_TL) was determined as a physiologically valid reference. ERD was also determined by wave separation (ERD_WSA) and pressure-only analyses (ERD_AW). Hemodynamic condition was changed by administrating zatebradine (bradycardic agent), nitroprusside, noradrenaline, dobutamine, and dextran. Results ERD_TL shortened significantly in response to infusion of nitroprusside or dobutamine. ERD_TL was significantly and negatively associated with AIx in multivariate analysis (Figure/Table). Changes in ERD_WSA or ERD_AW, and their association with AIx were not necessarily concordant with those observed in ERD_TL. Conclusion For the first time, we demonstrated that under diverse hemodynamic conditions, ERD_TL can change sensitively, and associates with AIx physiologically. This substantiates importance of tight attention to medication at clinical analysis of wave reflection phenomena. ERD_WSA or ERD_AW may not be a surrogate of ERD_TL. Responses of ERD to drugs Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science (JSPS)