Background: Until recently, the standard treatment for advanced malignant pleural mesothelioma (MPM) was only cisplatin plus pemetrexed. Nivolumab, an anti-programmed death-1 monoclonal antibody, shows efficacy against pretreated MPM and has been approved in Japan, but the data regarding the efficacy and safety of nivolumab in MPM are limited to those from a small number of patients of the MERIT study. Therefore, it is important to accumulate real-world data on the efficacy and safety of nivolumab for MPM. Methods: We retrospectively analyzed all patients with MPM who received nivolumab at Hyogo College of Medicine Hospital from August 2018 to December 2018. Results: A total of 77 patients (61 males and 16 females) were included. There were 62, 10, and 5 patients with performance statuses of 0–1, 2, and 3, respectively. There were 63, 8, and 6 patients with epithelioid, sarcomatoid, and bi-phasic histologies, respectively. Nivolumab was administered as second-, third-, and ≥fourth-line treatment to 48, 15, and 11 patients, respectively. In 66 patients who were examined for efficacy, the response rate (RR) was 24.2% and the disease control rate (DCR) was 63.6%. By the histology type, the RR and DCR were 15.1% and 62.3% for the epithelioid type, 62.5% and 87.5% for the sarcomatoid type, and 20.0% and 40.0% for the bi-phasic type, respectively. The median progression-free survival (mPFS) was 4.1 months and the median overall survival (mOS) was 13.3 months. Analyzing the efficacy based on the neutrophil-to-lymphocyte ratio (NLR) in the peripheral blood, the RRswere 14.7% in the NLR≥3.5 group and 25.8% in the NLR < 3.5 group. The mPFS and mOS in the NLR≥3.5 group were 3.1 months and 11.4 months, respectively,whereas those in the NLR < 3.5 group were 5.6 months and not reached, respectively. There were no significant differences in the RR, PFS, and OS between the groups, but a trend of better RRs and longer survivals wasobserved in the NLR < 3.5 group than in the NLR≥3.5 group. Regarding adverse events, fatigue (grades 1−2) was observed in 8, hypothyroidism (grade 1–2) in 11, renal dysfunction (grade 1–3) in 6, loss of appetite (grade 1–2) in 2, pneumonitis (grade 3) in 1, rash (grade 1) in 2, and hypopituitarism (grade 3) in 1 patient(s). Conclusions: This retrospective study revealed the effectiveness and safety of nivolumab for MPM in the real-world setting.Nivolumab can be used as a standard second-line treatment for MPM. Furthermore, it has been suggested that the NLR may be a predictive marker of the effect of nivolumab for MPM, as pointed out in other carcinomas.