Objectives: The aim of this study was to compare the treatment strategies of the original 500 pleural empyema patients from the REGIOMED clinics, in Germany, particularly regarding surgical management using minimally invasive surgery versus open thoracotomy. Specifically, the parameters of in-hospital mortality, postoperative stay, hospital readmission, and survival after one year were examined and compared. Materials and Methods: Originally, 500 patient data with the diagnosis of pleural empyema from the REGIOMED clinic network, spanning the period from 2017 to 2023, were retrospectively compared. During the analysis, some patients had to be excluded due to incomplete data. Various parameters were examined, focusing on the treatment options used in this study. The therapies were categorized into conservative therapy, drainage, minimally invasive surgery, open thoracotomy, and VAC therapy. Results: The study included a total of 344 patients with a median age of 66 years. In the examination of in-hospital mortality utilizing the Chi-square test, the findings revealed significant associations between conservative therapy and minimally invasive surgery with in-hospital mortality (P<0.001 and P<0.001, respectively). In terms of postoperative stay a significant difference (P=0.001) with a mean difference of 11.343 days was found between conservative and open surgery. Similarly, testing between minimally invasive and open surgery revealed a significant difference (P<0.001) with a mean difference of 10.319 days. The analysis of one-year survival rates revealed the overall one-year survival rate was 77.6% (256 out of 330 patients). While conservative and minimally invasive treatments showed statistically significant positive effects on one-year survival (P<0.001), open surgical treatment did not demonstrate a statistically significant impact. Overall, 18.1% (60 out of 332) of patients required hospital readmission due to pleural empyema or respiratory disease. While open surgical treatment showed a statistically significant association with higher readmission rates (P=0.001), conservative and minimally invasive treatments did not demonstrate any significant association with readmission rates. Conclusion: The minimally invasive therapy demonstrates statistical superiority in terms of hospital readmission, postoperative stay, and survival after one year compared to other treatment options. Nevertheless, it does not show superiority in terms of in-hospital mortality. The optimal treatment for a patient should be individualized and tailored to potential comorbidities and prognoses to guarantee quality of life.