This study evaluated health care worker exposure to antineoplastic drugs. A cross-sectional study examined environmental samples from pharmacy and nursing areas. A 6-week diary documented tasks involving those drugs. Urine was analyzed for two specific drugs, and blood samples were analyzed by the comet assay. Sixty-eight exposed and 53 nonexposed workers were studied. Exposed workers recorded 10,000 drug-handling events during the 6-week period. Sixty percent of wipe samples were positive for at least one of the five drugs measured. Cyclophosphamide was most commonly detected, followed by 5-fluorouracil. Three of the 68 urine samples were positive for one drug. No genetic damage was detected in exposed workers using the comet assay. Despite following recommended safe-handling practices, workplace contamination with antineoplastic drugs in pharmacy and nursing areas continues at these locations.