Background and AimAlthough the clinicopathological significance of the expression of programmed death ligand 1(PD‐L1) in various cancer tissues has been reported, serum PD‐L1 level has not been evaluated in patients with surgically treated gastric cancer. Therefore, we evaluated the clinicopathological characteristics and prognostic significance of preoperative serum PD‐L1 levels in patients with gastric cancer.Patients and MethodsSerum samples were obtained before surgery from 152 patients with gastric cancer, including 75 patients with stage I, 31 with stage II, 23 with stage III, and 23 with stage IV gastric cancer. The samples were analyzed using enzyme‐linked immunosorbent assay to detect soluble PD‐L1. Using the median serum PD‐L1 level of 50 pg/mL, patients were divided into two groups, namely high serum and low serum PD‐L1 level groups. Clinicopathological characteristics and prognosis were compared between these two groups using univariate and multivariate analysis.ResultsSerum PD‐L1 level was significantly associated with older age, positive cancer antigen 19‐9 (CA19‐9), C‐reactive protein levels, and albumin levels but not with tumor stage. Patients in the high serum PD‐L1 group showed significantly worse overall survival and recurrence‐free survival than those in the low serum PD‐L1 group (P < .05). Multivariate analysis showed that high serum PD‐L1 level was an independent risk factor for poor overall survival (P = .02).ConclusionHigh serum PD‐L1 level was a prognostic factor for reduced overall survival in patients with surgically treated gastric cancer.