Introduction: Electrostatic precipitation Pressurized IntraPeritoneal Aerosol Chemotherapy (ePIPAC) has shown superior penetration depth and tissue uptake compared to standard PIPAC. We investigated the feasibility and objective tumor response to ePIPAC with 1 min of precipitation in patients with peritoneal metastasis (PM). Materials and methods: Patients with PM from various abdominal cancers were included in an amendment to the ongoing prospective PIPAC-OPC2 trial. Colorectal and appendiceal PM were treated with oxaliplatin, patients with PM from other primaries were treated with a combination of cisplatin and doxorubicin. Three ePIPAC procedures were planned in each patient including repeated peritoneal biopsies for response evaluation. After emission to the peritoneal cavity, the aerosolized chemotherapeutics were precipitated for 1 min followed by immediate exsufflation and abdominal closure. Histological regression from the first to the third ePIPAC was evaluated according to the Peritoneal Regression Grading Score (PRGS) and compared to data from the PIPAC-OPC1 trial. Complications and toxicities were recorded according to Dindo-Clavien and CTCAE. Results: Sixty-five ePIPAC procedures were performed in 33 patients (median 2, range 1–6). Ten patients were eligible for response evaluation based on biopsies from the first and third ePIPAC procedure. Four patients had disease progression, four patients had regressive disease, and two patients had stable disease according to PRGS. No life threatening adverse reactions and no mortality was observed following ePIPAC. Conclusion: One minute ePIPAC was feasible and safe, but the histological tumor response was insufficient compared to standard PIPAC directed therapy with 30 min passive diffusion time.