Background: The preparation of injectable chemotherapy drugs is a critical process, given their toxicity and the large number of stakeholders involved. As such, systematic and proactive risk assessment is required. Objective: To analyze the risks associated with the cytotoxic drug preparation process using the failure mode, effects, and criticality analysis (FMECA) method within a centralized cytotoxic drug preparation unit (CCDPU). Methods: An analytical study was conducted in a CCDPU over a 6-month period. The risk analysis was performed using the FMECA method. An action plan was developed to address critical scenarios. A second FMECA cycle was conducted to evaluate the effectiveness of the implemented actions. Results: A total of 189 failure modes were identified, of which 2% were deemed unacceptable and 30% were tolerable when controlled. An action plan was developed based on training, double visual inspection, and the implementation of analytical control. During the follow-up FMECA, a reduction of 23% in the overall criticality index was observed, with a significant improvement in criticality levels. Of the 60 actions, 73% were completed, and an updated action plan was proposed. Conclusion: These results demonstrate the CCDPU team's genuine commitment to risk management and the usefulness of the FMECA method in a continuous improvement approach to the cytotoxic preparation circuit.