To assess the cost-effectiveness of blood cultures for patients with cellulitis, a retrospective review was conducted of clinical and microbiological data for all 757 patients admitted to a medical center because of community-acquired cellulitis during a 41-month period. Blood cultures were performed for 553 patients (73%); there were a total of 710 blood samples (i.e., a mean of 1.3 cultures were performed per patient). In only 11 cases (2.0%) was a significant patient-specific microbial strain isolated, mainly beta-hemolytic streptococci (8 patients [73%]). An organism that was considered a contaminant was isolated from an additional 20 culture bottles (3. 6%). The cost of laboratory workup of the 710 culture sets was $36, 050. Isolation of streptococci led to a change from empirical treatment with cefazolin to penicillin therapy for 8 patients. All patients recovered. In conclusion, the yield of blood cultures is very low, has a marginal impact on clinical management, and does not appear to be cost-effective for most patients with cellulitis.