Background/aims: To determine the role of thrombopoietin and spleen volume in thrombocytopenia diagnosed in cirrhotic and noncirrhotic portal hypertensive patients. Methods: Seventy-four portal hypertensive patients (group 1: 28 noncirrhotic; group 2: 46 cirrhotic) were enrolled into this study. Spleen volume was measured by magnetic resonance imaging. Thrombopoietin and hyaluronic acid. were detected by ELISA in sera. Results: Splenic volume was significantly higher in group 1 (1375 +/- 658.74 ml) than group 2 (981.78 +/- 512.39 ml). In group 1, thrombopoietin and hyaluronic acid levels were 76.6 +/- 30.39 pg/ml and 78.17 +/- 66.67 ng/ml, respectively. These values were significantly higher in group 2, at 99.89 +/- 38.5 pg/ml and 271.97 +/- 197.34 ng/ml, respectively (p<0.05). Platelet counts and thrombopoietin levels had a negative correlation with spleen volume in both groups (p<0.05). Serum thrombopoietin levels were not correlated with platelet counts in cirrhotic and noncirrhotic groups; however, thrombopoietin levels were negatively correlated with splenic volume in the whole group (p= 0.044, r= - 0.23). Although spleen volume was significantly larger in noncirrhotic patients, platelet counts were similar in both groups. Conclusions: This study confirms that splenic sequestration is the main factor in the thrombocytopenia in portal hypertensive patients. The balance of thrombopoietin production and degradation may be More important for platelet counts than decreasing synthesis.