Background: This phase I trial evaluated the safety and toxicity of laparoscopic hyperthermic intraperitoneal perfusion with chemotherapy (HIPEC) combining mitomycin, cisplatin, and paclitaxel for patients with gastric cancer metastatic to the peritoneum. Methods: A Bayesian optimal interval design was used to identify the maximum tolerated dose (MTD) of escalating doses of paclitaxel (starting dose of 20 mg/m2 to maximum dose of 60 mg/m2) in combination with flat doses of mitomycin (30 mg) and cisplatin (200 mg) during laparoscopic HIPEC for patients with gastric adenocarcinoma metastatic to the peritoneum. The primary endpoint was MTD. Secondary endpoints included surgical complications and overall survival (OS). Results: A total of 27 patients were treated from November 2017 through November 2018. No dose-limiting toxicities were found. Treatment-related grade 1-2 side effects were leukopenia (11%), oral dysesthesia (4%), arthralgia (4%), and diarrhea (4%). Treatment-related grade 3-4 side effects included leukopenia (4%) and neutropenia (4%). The MTD was 60 mg/m2. Clavien-Dindo surgical complications were grade I (all representing electrolyte deficiencies requiring replacement) in 96% of patients, grade II in 4%, grade III in 0%, grade IV in 0%, and grade V in 4%. At a median follow-up of 15 months, the median OS from diagnosis of metastatic disease and the date of surgery has not been reached. One- and 2-year OS rates from the date of metastatic disease were 74% and 58%, respectively. The 1-year OS rate from the date of HIPEC was 51%. Conclusions: Laparoscopic HIPEC with mitomycin, cisplatin, and paclitaxel appears safe at intraperitoneal doses of 30 mg, 200 mg, and 60 mg/m2, respectively. Although electrolyte abnormalities are common, systemic toxicity of this therapy is modest. Survival rates are promising, supporting further research into intraperitoneal therapy for stage IV gastric cancer. Clinical trial information: NCT03330028