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Purpose: The combination of acetaminophen with a nonsteroidal anti-inflammatory drug is the cornerstone of perioperative multimodal analgesia. These drugs can be administered intravenously or orally as premedication, consistent with the concept of pre-emptive and preventive analgesia. We aimed to assess the environmental impact of their intravenous and oral administration in a French university hospital. Methods: We carried out a life cycle assessment to determine the amount of greenhouse gas emissions and depletion of water resources resulting from the oral vsintravenous administration of 1 g acetaminophen and 50 mg ketoprofen. We assessed two schemes of intravenous administration, depending on the use of the same or a different infusion set for each drug. Results: At our centre, the intravenous administration of both drugs was associated with the emission of 444–556 g CO2equivalent (CO2e), and with 9.8–12.2 L of water waste. The oral administration of both drugs generated 8.36 g of CO2e emissions and consumed 1.16 L of water. At a national level, the switch from intravenous to oral premedication of the drugs could avoid the emission of 2,900–3,700 tons of CO2e and the waste of 58,000–74,000 m3of water each year. Conclusion: This eco-audit indicates that oral administration of acetaminophen and ketoprofen results in significantly lower carbon emissions and water consumption than intravenous administration. These findings highlight the importance of using the oral route for most patients, limiting intravenous administration for those with specific needs because of higher environmental impact and cost.