Main outcome was measured by procedure time, diagnostic accuracy, complication rate, time till stitches removal, average length of hospital stay and hospital cost. Results: SOPES was performed successfully in all 148 patients. 63 patients (90.0%) in the IM-group and 71 patients (91.0%) in the UM-group were clearly diagnosed. The inverse McBurney point approach was used in 70 cases, of which 63 (90.0%) yielded clear diagnoses, including malignant tumors (26 cases), tuberculosis peritonitis (24 cases), eosinophilic gastroenteritis (5 cases), liver cirrhosis (3 cases), Crohn's disease (1 case), connective tissue disease (1 case), primary hypothyroidism (1 case), Angiostrongylus Cantonensis (1 case), and POEMS syndrome (1 case). The umbilicus approach was used in 78 cases, of which 71 cases (91.0%) yielded clear diagnoses, including malignant tumors (38 cases), tuberculosis peritonitis (17 cases), liver cirrhosis (10 cases), eosinophilic gastroenteritis (3 cases), myelofibrosis (1 case), and nonspecific inflammation of peritoneum (2 case). The overall complication rate was 5.4% while the IM-group was lower than the UM-group (0% vs 10.3%, p<0.05). All complications were resolved after medical treatment and no mortality resulted from this procedure. The mean procedure time and time till stitches removal in the IM-group was shorter than that in the UM-group. When comparing the average length of hospital stay and hospital cost, there were no significant statistical difference. Conclusions: SOPES, a newly developed flexible endoscopic surgical modality, with strength of minimally invasive single orifice incision and flexible angles of examination and instrumentation, provides important new clinical valuable in evaluation of ascites of unknown origin. SOPES via the inverse McBurney's point was safer than the umbilicus approach.