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Background: The clinical use of software, specifically clinical decision support systems (CDSS) coupled with computerized provider order entry (CPOE) systems (CPOE/CDSS), has strong potential to improve chemotherapy treatment. Objective: The aim of this observational study was to evaluate whether the use of a CPOE/CDSS in chemotherapy treatment can improve dosing accuracy and/or expedite the patient intake process. Setting/Method: We conducted a month-long pilot implementation of a proprietary CPOE/CDSS called CenseoRx® at a large hospital in Athens, Greece. Anonymized chemotherapy dosage data, patient intake time, and time to log laboratory exams were recorded from 58 subjects. Main outcome measure: The therapeutic dosing decisions of physicians and of the software were compared. The time required to admit a new patient and the time required to log laboratory exams were recorded on the first and last week of the study period and compared. Results: A significant difference between the doctor-prescribed and the CPOE/CDSS-recommended dosage of the chemotherapeutic agents was observed for medications requiring body surface area (BSA)-based dosing, area under the curve (AUC)-based dosing, or weight-based dosing [mean difference = 18.42 mg chemotherapeutic agent, p = 0.0040] and for medications requiring solely AUC-based dosing [mean difference = 95.62 mg chemotherapeutic agent, p = 0.0295], with doctors under-prescribing the chemotherapeutic drug as compared to the CPOE/CDSS. A significant decrease in time needed for patient intake and for logging laboratory results was observed over the study period [mean difference = 121.5 s; mean difference = 89.0 s, respectively]. Conclusions: The implementation of a CPOE/CDSS can enhance the safety and quality of chemotherapy treatment. © 2022, The Author(s) under exclusive licence to International Union for Physical and Engineering Sciences in Medicine (IUPESM).