Background: Dental fear and uncooperative behavior can hinder dental treatment quality. Pediatric Procedural Sedation and Analgesia (PPSA) is used to facilitate treatment when the coping capacity is exceeded. Out-of-hospital PPSA has been associated with more adverse outcomes compared to when it is used in hospital-based settings. The updated Dutch PPSA guidelines have increased costs and raised concerns about the accessibility of specialized high-quality dental care for children in the Netherlands. This study aimed to investigate the impact of the updated 2017 guidelines on the occurrence rate of adverse events during PPSA in twelve Dutch dental clinics. Methods: The data of 25,872 children who were treated at twelve dental clinics between 1997 and 2019 were analyzed. A logistic two-level mixed-effects model was used to estimate the updated guidelines’ impacts on adverse events. Results: The OR of the occurrence rate of an adverse event adjusted for age, weight, and duration of treatment was 0.75 (95% CI 0.64–0.89) after the implementation of the updated guidelines. This outcome was significant with p = 0.001, indicating a protective effect. Conclusions: Our findings demonstrate that there was a significant reduction in adverse events after the implementation of the updated guideline and highlight the importance of adhering to evidence-based practices in out-of-hospital dental clinics.