BACKGROUND CONTEXTPerioperative allogeneic transfusion was generally considered to be safe. However, there had been some literatures reporting a potential association between surgical site infections (SSI) and blood transfusion. PURPOSETo determine whether perioperative blood transfusion increased the risk of SSI and to further explored whether there was a dose-response relationship. DESIGNRetrospective nested case-control study. PATIENT SAMPLEWe retrospectively analyzed consecutive patients who underwent spinal fusion surgery at our institution between July 2011 and July 2021. OUTCOME MEASUREIn the current study, the primary outcome measure was SSI. METHODSAll consecutive patients who underwent elective spinal surgery at our institution between July 2011 and July 2021 formed the retrospective cohort. Electronic patient record and radiographic data were reviewed retrospectively in our electronic database. To examine the effects of mismatched variables, we further adjusted for possible confounding factors using conditional logistic regression models. Then, we explored the nonlinear relationship between perioperative blood transfusion and SSI by a smoothed curve, with the adjustments for potential confounders. If a nonlinear relationship was observed, a two-piecewise regression model would be performed to calculate the threshold effect. RESULTSThe average time from surgery to diagnosis of SSI was 20.5 days. We matched 248 controls to 124 SSI cases. Of the 124 patients who developed SSI, 84 patients (67.7%) had deep SSI, 40 patients (32.3%) had superficial SSI. In the fully adjusted model, the risk of SSI increased by 27% for each additional unit of blood transfusion. It can be seen from the curve fitting plot that the risk of SSI has a greater increase after blood transfusion >3U. Subsequent piecewise regression identified an inflection point of 3U. CONCLUSIONWe determined that 3U was a threshold volume of allogeneic blood transfusion that shifted the risk of SSI following spinal surgery, and there was a dose-response effect.