Background: Since 2011, Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has emerged as a promising treatment option for patients with peritoneal surface malignancies (PSM) who are not eligible for cytoreductive surgery (CRS). Repeated minimal-invasive treatment is one of the key features and the current empirical standard treatment (ST) consists of at least three administrations over about three months. However, many patients are unable to complete the full course, limiting the potential benefits of PIPAC. Method: This retrospective, single-center study assessed the completion rate of ST and identified the main causes and predictive factors for discontinuation. This study also evaluated the feasibility, safety, and efficacy of PIPAC and investigated whether improved patient selection over the years has resulted in better oncological outcomes. Result: Data from 168 patients treated with PIPAC between January 2017 and March 2023 for a total of 336 procedures showed that only 29% completed ST. Multivariate analysis identified ascites >500 mL and a prior history of bowel obstruction as significant predictors of discontinuation. Conclusions: Patients with radiological or clinical signs of obstruction should not be considered for PIPAC treatment, and ascites increases the risk of incomplete treatment. Larger studies are eagerly awaited to corroborate these findings and refine the selection criteria by disease entity.