Postoperative delirium (POD) is a well-recognized postoperative complication and is associated with increased morbidity and mortality. We investigated whether the preoperative neutrophil-lymphocyte ratio (NLR) could be an effective predictor of POD after head and neck free-flap reconstruction. This was a single-center, retrospective, observational study. We analyzed the perioperative data of patients who had undergone elective head and neck free-flap reconstruction surgery. POD was assessed with the Intensive Care Delirium Screening Checklist (ICDSC) during admission to our intensive care unit (ICU). POD was defined as an ICDSC score ≥4. Risk factors for POD were evaluated by univariate and multivariate logistic regression analysis. We included 97 patients. The incidence of POD was 20.6% (20/97). Significantly longer ICU stays were observed in the patients with POD compared to those without POD (median [interquartile range]: 5 [4-6] vs. 4 [4-5], p = 0.031). Higher preoperative NLR values (3 <NLR ≤4 and 4 <NLR) were significantly associated with higher ICDSC scores compared to NLR ≤1 (4 [2-4] vs. 1 [1-1], p = 0.027 and 4 [1-4] vs. 1 [1-1], p = 0.038, respectively). The multivariable logistic regression analysis revealed that only a preoperative NLR >3.0 (adjusted Odds Ratio: 23.6, 95% Confidence Interval: 6.6-85.1; p<0.001) was independently associated with POD. The multivariate area under the receiver operator curve was significantly greater for the E-PRE-DELIRIC model with NLR compared to the E-PRE-DELIRIC model (0.87 vs. 0.60; p<0.001). The preoperative NLR may be a good predictor of POD in patients undergoing head and neck free-flap reconstruction.