Abstract Background Blood culture contamination (BCC) has been associated with prolonged antibiotic use (AU) and increased health care utilization; however, this has not been widely reevaluated in the era of increased attention to antibiotic stewardship. We evaluated the impact of BCC on AU, resource utilization, and length of stay in Dutch and US patients. Methods This retrospective observational study examined adults admitted to 2 hospitals in the Netherlands and 5 hospitals in the United States undergoing ≥2 blood culture (BC) sets. Exclusion criteria included neutropenia, no hospital admission, or death within 48 hours of hospitalization. The impact of BCC on clinical outcomes—overall inpatient days of antibiotic therapy, test utilization, length of stay, and mortality—was determined via a multivariable regression model. Results An overall 22 927 patient admissions were evaluated: 650 (4.1%) and 339 (4.8%) with BCC and 11 437 (71.8%) and 4648 (66.3%) with negative BC results from the Netherlands and the United States, respectively. Dutch and US patients with BCC had a mean ± SE 1.74 ± 0.27 (P < .001) and 1.58 ± 0.45 (P < .001) more days of antibiotic therapy than patients with negative BC results. They also had 0.6 ± 0.1 (P < .001) more BCs drawn. Dutch but not US patients with BCC had longer hospital stays (3.36 days; P < .001). There was no difference in mortality between groups in either cohort. AU remained higher in US but not Dutch patients with BCC in a subanalysis limited to BC obtained within the first 24 hours of admission. Conclusions BCC remains associated with higher inpatient AU and health care utilization as compared with patients with negative BC results, although the impact on these outcomes differs by country.