Introduction. Adequate sedation and analgesia is essential in the management of patients requiring mechanical ventilation (MV). The implementation of protocols and their monitoring is recommended; mixed results on adherence and impact have been reported. Objectives. To assess the impact of the implementation of a sedation and analgesia protocol on the use of benzodiazepines, opioids, and evolution in the pediatric intensive care unit (PICU) in patients requiring MV for more than 72 hours. Methods. Before-and-after, uncontrolled study in the PICU of a children’s hospital. The study was developed in 3 stages: pre-intervention for situational diagnosis (from April to September 2019), intervention,and post-intervention for implementation of a sedation and analgesia protocol, education on use, and monitoring of adherence and impact (from October 2019 to October 2021). Results. A total of 99 and 92 patients were included in the study in the pre- and post-intervention stages, respectively. Patients had a more severe condition, were younger, and had a lower weight in the preintervention period. After adjusting for severity and age, the group comparison in the post-intervention stage showed a reduction in days of continuous infusion of opioids (6 ± 5.2 versus 7.6–5.8, p = 0.018) and days of continuous infusion of benzodiazepines (3.3 ± 3.5 versus 7.6 ± 6.8, p = 0.001). No significantdifferences were observed in days of MV and total days of benzodiazepine use. Conclusion. The implementation of a sedation and analgesia protocol resulted in a reduction in the use of continuous infusion of drugs.