Aims: Surgical site infections contribute to morbidity and mortality after surgery. The authors hypothesized that higher antibiotic tissue concentrations can be reached for a prolonged time span by continuous administration of prophylactic cefuroxime compared to bolus administration. Methods: Twelve patients undergoing elective cardiac surgery were investigated. Group A received 1.5 g cefuroxime as bolus infusions before surgery, and 12 and 24 hours thereafter. In group B, a continuous infusion of 3.0 g cefuroxime was started after a bolus of 1.5 g. Cefuroxim levels were determined in blood and tissue (microdialysis). T‐test, Wilcoxon signed rank test and χ2 test were used for statistical analysis. Results: The area under the curve (AUC) of plasma cefuroxime concentrations was greater in group B (399 [333–518]) as compared to group A (257 [177–297] h mg L−1, [median and interquartile range], P = .026). Furthermore, a significantly longer percentage of time > minimal inhibitory concentrations of 2 mg L−1 (100% vs 50%), 4 mg L−1 (100% vs 42%), 8 mg L−1 (100% vs 17%) and 16 mg L−1 (83% vs 8%) was found for free plasma cefuroxime in group B. In group B, area under the curve in subcutaneous tissue (78 [61–113] h mg L−1) and median peak concentration (33 [26–38] mg L−1) were markedly higher compared to group A (P = 0.041 and P = .026, respectively). Conclusions: Higher cefuroxime concentrations were measured in plasma and subcutaneously over a prolonged period of time when cefuroxime was administered continuously. The clinical implication of this finding still has to be elucidated. [ABSTRACT FROM AUTHOR]