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Introduction: Gastrointestinal tract cancers are the most common cancers in Iran with a growing incidence in the past two decades, especially in the Northern provinces of the country. Different chemotherapy regimens have been used in the treatment of colorectal cancers (CRC). Considering lack of data, this study aimed to determine the adverse drug reactions (ADRs) of chemotherapy regimens used in treatment of patients with CRC. Material and methods:This cross-sectional prospective study was carried out in Emam Khomeini Hospital and Tooba Clinic, both affiliated to Mazandaran University of Medical Sciences. ADRsof chemotherapy regimens including nausea, vomiting, fever and neutropenia, diarrhea, oral mucositis, neuropathy and hair loss were documented based on CTCAE Version 4.0 (Common Terminology Criteria for Adverse Events). Results:Two hundred sixty seven different courses of chemotherapy regimens received by 48 patients were evaluated in terms of adverse events. Three more common chemotherapy regimens wereFOLFOX (Folinic acid, Fluorouracil, Oxaliplatin), FOLFIRI (Folinic acid, Fluorouracil, Irinotecan) and XELOX (Capecitabine, Oxaliplatin).FOLFIRI and FOLFOX regimens were associated with more nausea and vomiting compared to XELOX. The rate of vomiting was marginally different between regimens (P=0.06). Most of nausea and all vomiting were as grade 1 or 2. The diarrhea was more common with FOLFOX (P=0.027). Whereas 14% of patients received FOLFIRI experienced neutropenia, none of patients in XELOX and almost 5% of FOLFOX patients experienced neutropenia. Mucositis happened in 16.1 and 17.8% of patients received FOLFOX and XELOX, respectively. The rate of neuropathy was different among regimens, as XELOX and FOLFOX were associated with more neuropathy compared with FOLFIRI (P=0.019). The rate of hair loss and headache were not different between three regimens.Most of the side effects (e.g., nausea, neuropathy, and headache) were acute. Vomiting and mucositis with XELOX occurred after 24 hours of initiation of chemotherapy. Conclusion:The results of our study showed that the GI adverse events including nausea, vomiting and severe diarrhea were more common with FOLFIRI regimen. Mucositis and neuropathy were more common with XELOX. Hair loss was more common with FOLFIRI followed by XELOX and FOLFOX.