Background: Medication errors occur frequently and may potentially harm patients. Administering medication with infusion pumps carries specific risks, which lead to incidents that affect patient safety. Objective: Since previous attempts to reduce medication errors with infusion pumps failed in our intensive care unit, we chose the Lean approach to accomplish a 50% reduction of administration errors in 6 months. Besides improving quality of care and patient safety, we wanted to determine the effectiveness of Lean in healthcare. Methods: We conducted a before-and-after observational study. After baseline measurement, a value stream map (a detailed process description, used in Lean) was made to identify important underlying causes of medication errors. These causes were discussed with intensive care unit staff during frequent stand-up sessions, resulting in small improvement cycles and bottom-up defined improvement measures. Pre-intervention and post-intervention measurements were performed to determine the impact of the improvement measures. Infusion pump syringes and related administration errors were measured during unannounced sequential audits. Results: Including the baseline measurement, 1748 syringes were examined. The percentage of errors concerning the administration of medication by infusion pumps decreased from 17.7% (95% confidence interval, 13.7–22.4; 55 errors in 310 syringes) to 2.3% (95% confidence interval, 1–4.6; 7 errors in 307 syringes) in 18 months (p < 0.0001). Conclusion and Relevance: The Lean approach proved to be helpful in reducing errors in the administration of medication with infusion pumps in a high complex intensive care environment.