Retrograde autologous priming (RAP) is a process used to reduce hemodilution associated with the initiation of cardiopulmonary bypass (CPB). Previous studies have reported potential benefits to RAP; however, many of these studies do not evaluate the benefits of RAP with limited preoperative fluid administration combined with a condensed CPB circuit. We examined clinical metrics of patients who underwent RAP versus those who did not undergo RAP prior to the initiation of CPB. This was a retrospective data review of 1,303 patients who underwent CPB in the setting of open-heart surgery for a 2-year period. RAP was used on all patients between June 1, 2017 and June 30, 2018 (n = 519) and not used on patients between July 1, 2018 and June 30, 2019 (n = 784). Both groups were subjected to a low-prime CPB circuit volume of 800-900 mL. We compared the clinical metrics for packed red blood cell (PRBC) transfusion, oxygen delivery, postoperative acute kidney injury (AKI), Albumin utilization, ventilator time, Intensive Care Unit length of stay (ICU LOS), and 30-day mortality between the two groups. Our data analysis showed there were no statistically significantly differences between the two groups on the incidence of postoperative AKI, PRBC administration, ventilator time, ICU LOS or 30-day mortality. In the RAP group, there was a statistically significant lower oxygen delivery and a statistically significant increased volume of Albumin administered postoperatively, although those differences were so small, they were potentially not clinically significant. Our analysis revealed no significant benefit to performing RAP with limited preoperative fluid administration and minimized CPB circuit prime volume. We formalized a process that included limiting preoperative fluid administration and minimizing the CPB circuit volume so that we were not required to RAP and did not simultaneously sacrifice patient outcomes in other areas.