Background: Surgery for malignant pleural mesothelioma (MPM) is indicated mainly in multimodal approaches and in clinical trial settings. Different studies have shown significantly lower complication rates, lower peri-operative morbidity and mortality with pleural/decortication (P/D), with similar overall survival rates. The biology of mesothelioma shows significant heterogeneity. Surgical tumor reduction may create a host environment more amenable to immunotherapy by reducing the ratio of tumor cells versus antitumor effector T lymphocytes, reducing the quantities of intratumor and/or systemic immunosuppressive cells, and ablating tumor-derived paracrine factors that promote local recruitment of immunosuppressive cells. Encouraging clinical data emerging in the field of tumor immunotherapy have demonstrated that therapies focused on enhancing T-cell responses against cancer can result in a significant survival benefit. The AtezoMeso Study evaluates the introduction of atezolizumab-ATEZO in MPM, patients (pts) after P/D and platinum/pemetrexed perioperative therapy. Methods: This is a double-blind, placebo controlled, phase III trial, in 20 Italian centers. Main inclusion criteria are P/D without macroscopic residual and ECOG-PS 0-1. Pts who underwent to P/D without macroscopic residual disease and have received at least 4 cycles of perioperative therapy with cisplatin/carboplatin and pemetrexed, will be randomized (2:1) to receive ATEZO or placebo. Therapy will be administered at dose of 1,200 mg iv, every 21 days, for 12 months or until recurrence, unacceptable toxicity or patient/physician decision. Randomization will be done through a centralized system, using histology (epithelioid vs nonepithelioid) and stage (I vs > I) as stratification factors. Pts will be radiologically evaluated after surgical before starting therapy and then every 12 weeks for 24 months or until recurrence. Quality of life (QoL) will be evaluated with the EQ-5D questionnaire administered at baseline and every 12 weeks. Tissue tumor samples will be centrally analyzed to determinate the genomic profile using FoundationOne CDx platform. The primary endpoint is the evaluation of the atezolizumab efficacy in terms of disease free survival (DFS). Secondary endpoints include the safety and efficacy in terms of overall survivall and QoL. Assuming a median DFS equal to 9 months in placebo arm, an accrual time of 24 months and a follow-up time of 24 months, a sample size of 162 pts will allow to detect true hazard ratios of 0.62 with power 0.8, at a confidence level of 95%. At February 14^th, 2022, 3 pts have been enrolled. Clinical trial information: 2020-003762-39; GOIRC-02-2019.