Objectives: For treating advanced or recurrent cancer with peritoneal carcinomatosis, Pressurized Intraperitoneal Aerosol Chemotherapy has been introduced, which is considered as safe treatment without detectable aerosol leakage. Although we developed a novel prototype of Rotational Intraperitoneal Pressurized Aerosol Chemotherapy (RIPAC) for improving the distribution and depth of penetration of drugs, its occupational safety has not been investigated. This study aimed to investigate potential exposure to health care workers during RIPAC using a hydrophobic agent such as doxorubicin, cisplatin, paclitaxel and cremophor-free polymeric micelle formulated paclitaxel. Methods: As 10% doses for intravenous chemotherapy, doxorubicin of 3 mg, cisplatin of 10 mg, paclitaxel of 30mg, and cremophor-free polymeric micelle formulated paclitaxel of 30 mg were administered with 0.9% NaCl of 50 ml as an aerosol by RIPAC in every three pigs. For preventing aerosol leakage during RIPAC, we used an air-tight trocar and the entire procedure was remotely controlled. Toxic aerosols were eliminated through microparticle filters, and the operating room was equipped with laminar airflow. A sampling of toxic aerosol in the air was performed in breathing zones of operators, anesthesiologists, and scrub nurses, as well as at the entrance of the operating room. Numbers of airborne particles were also assessed to detect potential leakage from the laparoscopic instrument and airborne diffusion. Results: In off-line measurement, we found no detection of leakage during RIPAC using doxorubicin, cisplatin, and cremophor-free polymeric micelle formulated paclitaxel in the air (Limit of detection, LOD, 1.28 ng/ml, 0.772 ng/sample, and 5.68 ng/ml, respectively), while paclitaxel was detected in samples of 75% (LOD, 36.5 ng/sample). In one-line measurement, there was no cumulative risk of leakage of airborne particles during repetitive RIPAC procedures using doxorubicin, cisplatin, and cremophor-free polymeric micelle formulated paclitaxel except increased numbers of airborne particles induced by movements of medical staff. Conclusions: Air contamination of doxorubicin, cisplatin, and cremophor-free polymeric micelle formulated paclitaxel was below the detection limit in the air along with steady levels of numbers of the airborne particles during repetitive RIPAC procedures, suggesting the occupational safety of RIPAC using these three agents. However, paclitaxel may require caution during RIPAC because of a relatively high detection in the air. For treating advanced or recurrent cancer with peritoneal carcinomatosis, Pressurized Intraperitoneal Aerosol Chemotherapy has been introduced, which is considered as safe treatment without detectable aerosol leakage. Although we developed a novel prototype of Rotational Intraperitoneal Pressurized Aerosol Chemotherapy (RIPAC) for improving the distribution and depth of penetration of drugs, its occupational safety has not been investigated. This study aimed to investigate potential exposure to health care workers during RIPAC using a hydrophobic agent such as doxorubicin, cisplatin, paclitaxel and cremophor-free polymeric micelle formulated paclitaxel. As 10% doses for intravenous chemotherapy, doxorubicin of 3 mg, cisplatin of 10 mg, paclitaxel of 30mg, and cremophor-free polymeric micelle formulated paclitaxel of 30 mg were administered with 0.9% NaCl of 50 ml as an aerosol by RIPAC in every three pigs. For preventing aerosol leakage during RIPAC, we used an air-tight trocar and the entire procedure was remotely controlled. Toxic aerosols were eliminated through microparticle filters, and the operating room was equipped with laminar airflow. A sampling of toxic aerosol in the air was performed in breathing zones of operators, anesthesiologists, and scrub nurses, as well as at the entrance of the operating room. Numbers of airborne particles were also assessed to detect potential leakage from the laparoscopic instrument and airborne diffusion. In off-line measurement, we found no detection of leakage during RIPAC using doxorubicin, cisplatin, and cremophor-free polymeric micelle formulated paclitaxel in the air (Limit of detection, LOD, 1.28 ng/ml, 0.772 ng/sample, and 5.68 ng/ml, respectively), while paclitaxel was detected in samples of 75% (LOD, 36.5 ng/sample). In one-line measurement, there was no cumulative risk of leakage of airborne particles during repetitive RIPAC procedures using doxorubicin, cisplatin, and cremophor-free polymeric micelle formulated paclitaxel except increased numbers of airborne particles induced by movements of medical staff. Air contamination of doxorubicin, cisplatin, and cremophor-free polymeric micelle formulated paclitaxel was below the detection limit in the air along with steady levels of numbers of the airborne particles during repetitive RIPAC procedures, suggesting the occupational safety of RIPAC using these three agents. However, paclitaxel may require caution during RIPAC because of a relatively high detection in the air.