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Protein phosphatase magnesium-dependent 1 delta (PPM1D) has recently been associated with tumor biology. However, the expression pattern and clinical significance of PPM1D in gastric cancer (GC) have yet to be elucidated. The present study aimed to investigate the clinical and prognostic significance of PPM1D in GC. PPM1D expression was assessed in 800 patients with GC using immunohistochemistry and tissue samples were divided into a PPM1D-positive and -negative group. The correlation between PPM1D expression and clinicopathological parameters or prognosis was investigated. PPM1D expression was significantly higher in GC tissue than in adjacent normal tissue (48 versus 9.5%; P<0.001). PPM1D positivity was significantly correlated with nodal status, distant metastasis and vascular invasion. Survival analysis indicated that the five-year survival rate in the PPM1D-positive group was significantly lower than that in the PPM1D-negative group (41 versus 72%; p=0.0012). Furthermore, the association between PPM1D positivity and survival rate was still significant following regulation of other prognostic markers in a multivariate analysis [hazard ratio (HR), 6.572; 95% confidence interval (CI), 3.108-13.471; P=0.0018]. In conclusion, the present study suggested that PPM1D positivity is associated with GC invasion and metastasis, and proposed PPM1D positivity as an indicator of unfavorable prognosis in patients with GC. [ABSTRACT FROM AUTHOR]