Background: Pleural effusion and empyema are frequent complications of acute bacterial pneumonia in children. To date, evidence regarding the optimal treatment of this condition is limited in the literature. Methods: Patients with pleural effusion and empyema admitted at our Pediatric Surgery Department over the last ten years were enrolled in this retrospective study, and successively compared with the clinical charts of patients treated before the introduction of a new diagnostic and therapeutic algorithm. Results: After the introduction of the new algorithm there were a decrease in the use of chest radiography for re-evaluation (100% vs. 79%, p = 0.003), a more focused use of CT (68% vs. 15%, p = 0.001), and a decrease in the use of a second CT (18% vs. 3%, p = 0.07); in favor of an increase in the use of the US scan (40%vs 100%, p=0.001). There was also a shift from the use of chest tube drainage alone to the use of drainage for Urokinase administration (50% vs. 92.3%, p = 0.001), and a statistically significant decrease in the need for video-assisted thoracoscopic surgery (25% vs. 7.7%, p = 0.001). Conclusions: The introduction of a diagnostic and therapeutic algorithm for the management of pediatric pleural effusion and empyema has notably resulted in a decrease in the utilization of radiography and computed tomography and an increase in the use of ultrasonography, reducing unnecessary radiation exposure in children and overall costs.