Background: Prior literature has examined the association between preoperative anemia and complications across surgical settings; however, evidence is lacking for splenectomy patients. We investigated the association between preoperative hematocrit and 30-day postoperative outcomes in this population using a national database. Methods: Patients who underwent splenectomy (2012–2017) were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Analyses were performed for the overall cohort and elective versus emergent subsets, adjusting for transfusion among other covariates. Results: Our sample included 5,580 patients. As hematocrit decreased, complication rates increased incrementally in both the univariate and multivariate analyses. Adjusted odds ratios (and 95% confidence intervals) for moderate anemia (26% ≤ hematocrit < 30%) as compared to no anemia (hematocrit ≥ 38%) were readmission = 1.5 (1.1–1.8), sepsis = 2.2 (1.6–3.0), and composite outcome = 1.8 (1.0–3.2). Parameter estimates (standard error, P value) for the moderate versus no anemia group were length of stay = 3.0 (0.5, P < .001) and days to discharge = 1.2 (0.3; P < .001). Conclusion: Our results demonstrate a dose-response relationship between increasing degree of anemia and odds of various postoperative adverse outcomes after adjusting for several potential confounders. The subset analysis further suggests that elective splenectomy cases are more likely to have poor outcomes when in the presence of anemia or when transfusions are performed as compared to emergent cases. This suggests that the harm associated with transfusion may offset the benefit of optimizing anemia in an elective splenectomy case.