Background: Although tumor markers are known to be associated with tumor burden and/or aggressive biology, any association of such markers with patient survival has not previously been determined in patients with metastatic or recurrent gastric cancer. Methods: Of 3,107 patients with metastatic or recurrent gastric cancer who initiated palliative chemotherapy in Asan Medical Center between January 2000 and December 2008, 1,178 were assayed for expression of three serum tumor markers, CA 19-9, CA 72-4, and CEA, prior to initiation of first-line chemotherapy. We retrospectively analyzed the relationships between tumor marker concentrations and clinicopathologic features, and treatment outcomes in such patients. Results: Elevated serum concentrations of CA 19-9 (>37 U/mL), CA 72-4 (>4 U/mL), or CEA (>6 ng/mL) were observed in 38.1%, 56.2%, and 33.1% of patients, respectively. Univariate analysis showed that serum positivity of all the 3 markers, CA 19-9 (p=0.001), CA 72-4 (p=0.001), and CEA (p=0.030) were associated with poor survival. However, upon multivariate analysis, only CA19-9 (HR 1.22; 95% CI, 1.08-1.37, p<0.001) was independently associated with poor survival outcome, in addition to the following clinical factors determined in previous study for gastric cancer prognostic model (Koo, et al): ECOG PS ≥ 2, no previous gastrectomy , peritoneal metastasis, bone metastasis , lung metastasis, serum alkaline phosphatase (ALP) > 120 IU/L, serum albumin < 3.3 g/dL, and total serum bilirubin > 1.2 mg/dL. In good risk group by the prognostic model, survival difference in the positivity of CA 19-9 was more significant (p < 0.001), while serum positivity of CA 19-9 did not provide clinical significance for moderate and poor groups. Conclusions: The postivitiy of serum CA 19-9 for patients with metastatic or recurrent gastric cancer at the time of first line chemotherapy, especially in good prognostic group is an independent negative prognostic factor.