Objective: To investigate the value of preoperative plasma levels of D-dimer (D-D) and fibrinogen (FIB) in predicting the postoperative prognosis of patients with gastrointestinal stromal tumor (GIST). Methods: The clinicopathologic and follow-up data of patients with GIST undergoing surgical treatment from January 2010 to December 2015 were collected. The relations of preoperative D-D and FIB levels with the prognosis of patients were analyzed. Results: Of the 170 GIST patients, 91 cases were male and 79 cases were female, ages mainly ranged from 50 to 70 years, and the primary tumors were mostly located in the stomach (122 cases, 71.8%) followed by the small intestine (34 cases, 20.0%). The 3- and 5-year recurrence free survival rate (RFS) of the entire group was 85% and 75%, respectively. The ROC curves with survival outcome (occurrence of metastasis or recurrence) as state variable demonstrated that the optimal cut-off point for D-D and FIB was 1.24 mg/L and 3.24 g/L, respectively. Univariate analysis showed that D-D≥1.24 mg/L, FIB≥3.24 g/L, moderate and high NIH risk categories, tumor diameter greater than 5 cm, and extra-gastric location were significantly associated with the reduced postoperative 3- and 5-year RFS of GIST patients (all P<0.05); multivariate analysis revealed that D-D (RR=0.382, 95% CI=0.151–0.967, P=0.042), FIB (RR=0.123, 95% CI=0.035–0.430, P=0.001) and tumor NIH risk category (RR=0.149, 95% CI=0.042–0.524, P=0.003) were independent risk factors for postoperative prognosis of GIST patients. There was significant correlation between tumor NIH risk category and either D-D or FIB in GIST patients (r=0.648; 0.868, both P<0.01). Conclusion: Preoperative plasma levels of D-D and FIB can potentially be used as predictors for postoperative outcome of GIST patients.