Background: Salivary gland cancer is rare and has various pathological subtypes. With this rarity and heterogeneity, the therapeutic contribution of chemotherapy, including immune checkpoint inhibitors, for recurrent or metastatic salivary gland cancer (RM-SGC) has not been elucidated. The purpose of this trial was to investigate the efficacy and safety of nivolumab for patients with platinum-refractory RM-SGC. Methods: This open-label, single-arm, multicenter phase II trial was conducted at 9 centers in Japan. Eligible patients had platinum-refractory recurrent or metastatic salivary gland cancer with measurable lesions by RECIST v1.1 and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, or 2. Nivolumab 240 mg/body was administered intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). We set the null hypothesis at 3% and the expected at 15% with a one-sided alfa of 0.1 and power of 80%. Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Twenty-four patients (16 males; median age, 65.5 years [range, 34-78 years]) were enrolled between March 2018 and January 2022. Pathological types were salivary duct carcinoma (n = 10), adenoid cystic carcinoma (n = 6), adenocarcinoma not otherwise specified (n = 5), mucoepidermoid carcinoma (n = 2), and acinic cell carcinoma (n = 1). In the majority of cases the primary site was a major salivary gland (n = 21), namely the parotid gland in 16 patients and submandibular gland in 5. The primary endpoint of ORR was 8.3% (2/24, 80% CI, 2.2-20.6%), with 2 partial responses (PR) in patients with salivary duct carcinoma (2/10, ORR: 20.0%). DCR was 29.2% (7/24, 2 in PR and 5 in stable disease), and all of the other 17 patients（70.8%）showed progressive disease (PD) on first disease evaluation at 12 weeks. With a median follow up for survivors of 32.0 months, median PFS and OS were 3.0 months (95% CI, 2.8-3.2 months) and 25.0 months (95% CI, 10.9-39.1 months), respectively. There was no new safety concern with nivolumab monotherapy. Conclusions: This phase II trial of nivolumab monotherapy for patients with platinum-refractory RM-SGC did not meet its primary endpoint of ORR. Although nivolumab monotherapy may be worth further development in salivary duct carcinoma, these results may raise concerns over nivolumab monotherapy for RM-SGC. Translational research to elucidate the immune microenvironment of each pathological type is under investigation. Clinical trial information: UMIN000029636.