Background: The management of esophageal cancer (EC) and gastroesophageal junction (GEJ) adenocarcinoma has focused on perioperative approaches that aim to increase pathological complete response (pathCR) rates, decrease or delay metastases, improve resectability, and enhance overall survival. Atezolizumab is a humanized immunoglobulin (Ig) G1 monoclonal antibody that targets PD-L1 and inhibits the interaction between PD-L1 and its receptors, PD-1, and B7-1, both of which function as inhibitory receptors expressed on T-cells. Therapeutic binding of PD-L1 by atezolizumab has been shown to enhance the magnitude and quality of tumor-specific T-cell responses, resulting in improved anti-tumor activity. The use of immunotherapy in combination with chemotherapy in the perioperative setting may improve the response rate in patients with localized EC and GEJ adenocarcinoma. Methods: We conducted a phase I study evaluating the efficacy and safety of atezolizumab in combination with oxaliplatin and 5-fluorouracil (modified FOLFOX) therapy in the perioperative setting. Patients with T1N1 or T2-3 (any N) localized EC and GEJ type I or II adenocarcinoma were included. Treatment consisted of oxaliplatin (85 mg/m2 over 2 hours on days 1 and 15) and 5-fluorouracil (2.4g/m2 (over 48 hours) via infusion pump on days 1 and 15) followed by atezolizumab (840 mg via IV on days 1 and 15) of each 28-day cycle for a total of 6 doses followed by surgery and subsequently postoperative atezolizumab 1200 mg IV on Day 1 of each 21-day cycle for 8 more doses. Results: From April 2019 to November 2020, 20 patients were enrolled with a median age of 61 years old and baseline TNM staging: T2-3N0 (n=8), T3N1-N2 (n=10), and T3N3-NX (n=2). Eighteen patients underwent surgery; two patients (11%, 95% credible interval = 1-28%) achieved the primary efficacy objective (pathCR defined as pathological T0N0), and two additional patients (11%) had near complete pathCR with <1% viable tumor. Fifteen patients (83%) had R0 resection. Grade 4 treatment-related events occurred in 2 patients and grade 2 and 3 treatment related events occurred in 9 and 7 patients respectively. No treatment-related events leading to discontinuation of therapy or treatment-related deaths occurred. Forty-five percent of the patients died and 44% of patients had recurrence with a median disease-free survival of 29 months. Conclusions: Results indicate that atezolizumab in combination with oxaliplatin and 5-fluorouracil has an acceptable safety profile providing high tumor regression. This trial supports further research of atezolizumab for the treatment of patients with localized EC and GEJ in the perioperative setting. Clinical trial information: NCT03784326.