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Objectives: To evaluate environmental contamination with methotrexate, cyclophosphamide, and ifosfamide in Quebec, Canada, community pharmacies and to describe hazardous drug handling practices in these pharmacies. Methods: Three standardized sites were sampled in each participating community pharmacy. Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by high-performance liquid chromatography tandem mass spectrometry. The limits of detection were 0.10, 0.12, and 0.41 ng/mL for cyclophosphamide, ifosfamide, and methotrexate, respectively. Nine working practices were assessed. Results: 20 community pharmacies participated in the study, and 60 samples were analyzed. No traces of cyclophosphamide or ifosfamide were detected. Traces of methotrexate were found in 12 of 20 pharmacies (60%). Of the 20 pharmacies, 8 (40%) had a storage space reserved for hazardous drugs and none had a preparation area reserved for handling methotrexate tablets. All of the participating community pharmacies had a tablet counter reserved for the handling of hazardous drugs, and all pharmacies cleaned their tablet counter reserved for handling hazardous drugs after use. None of the pharmacies cut or crushed methotrexate tablets. Conclusion: The growing number of hazardous drugs represents a challenge for community pharmacies. Community pharmacists must be made aware of their presence and the need to comply with personal protection measures to reduce staff occupational exposure to hazardous drugs.