To study the effect of transfusion on recurrence of squamous cell carcinoma of the head and neck, we analyzed the records of 143 patients with stage II through IV squamous cell carcinoma of the supraglottic larynx or hypopharynx for whom follow-up to recurrence or 5 years after surgical therapy was available. Variables studied were age, gender, TNM staging, duration of operation, estimated blood loss, units of blood products transfused, surgical margins, number of pathologic nodes, radiotherapy, chemotherapy, hematocrit, and serum albumin. Multivariate logistic regression demonstrated that transfusion, number of pathologic nodes, and preoperative hematocrit were significantly related to recurrence. The univariate odds ratio for tumor recurrence in patients receiving any blood products was 3.2 (95% confidence interval 1.5 to 6.9; p = 004). Based on a meta-analysis of the data from this study and the five published studies, the combined odds ratio for recurrence after transfusion was 2.6 (95% confidence interval 1.9 to 3.7; p < 0001). These data identify a clinically important adverse effect of transfusion of blood products on tumor recurrence in patients with advanced head and neck cancer. We recommend a policy of blood conservation surgery to enhance cancer control, and we encourage further research to clarify the mechanism(s) of this effect. © 1992, SAGE Publications. All rights reserved.