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Purpose-Surface contamination with the antineoplastic drugs cyclophosphamide, ifosfamide, and 5-fluorouracil was compared in 22 US hospital pharmacies following preparation with standard drug preparation techniques or the PhaSeal ® closed-system drug transfer device (CSTD).Methods-Wipe samples were taken from biological safety cabinet (BSC) surfaces, BSC airfoils, floors in front of BSCs, and counters and analyzed for contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil. Contamination was reassessed several months after the implementation of the CSTD. Surface contamination (ng/cm 2 ) was compared between the two techniques and evaluated with the Signed Rank Test.Results-Using the CSTD compared to the standard preparation techniques, a significant reduction in levels of contamination was observed for all drugs (cyclophosphamide: p <0.0001; ifosfamide: p <0.001; 5-fluorouracil: p <0.01). Median values for surface contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil were reduced by 95%, 90%, and 65%, respectively.Conclusions-Use of the CSTD significantly reduces surface contamination when preparing cyclophosphamide, ifosfamide, and 5-fluorouracil as compared to standard drug preparation techniques.Reprints and permissions: sagepub.co.uk/journalsPermissions.nav Corresponding author: Dr. Paul J.M. Sessink, Exposure Control B.V.,