ABSTRACT Purpose: Meconium aspiration syndrome as one of the devasting conditions which remains the major cause of neonatal morbidity and mortality. Preterm infants affected by this life-threatening disease did not get enough attention. The aim of this study was to identify risk factors associated with mortality of preterm infant hospitalized with meconium aspiration syndrome. Methods: We undertook a case-control study in a neonatal diagnosis and treatment center in China over a ten-year period. Preterm newborns affected by meconium aspiration syndrome with early onset of respiratory distress hospitalized in NICU were included. Variables were compared between the non-survival group and survival group. Logistic regression model was conducted to identify risk factors associated with mortality. Results: Totally 92 preterm infants were included, 31(33.7%) died. Their median gestational age was 33.4 weeks, and their mean birth weight was 1925.2 g. Female[19(61.3%) vs 18(29.5%), P=0.003], arterial blood pH[7.22(±0.13) vs 7.30(±0.12), p=0.008], persistent pulmonary hypertension[19(61.3%) vs 21(34.4%), P=0.014], and pulmonary hemorrhage[16(51.6%) vs 13(21.3%), P=0.003] were associated with an increased rate of mortality. In the logistic regression model, the risk of death were found to be statistically associated with the following three factors: Female [odds ratio (OR) 3.91; 95% confidence interval(CI) (1.37-11.16); P=0.011], persistent pulmonary hypertension [OR 3.12; 95% CI (1.10-8.89); P=0.033], and pulmonary hemorrhage [OR 4.36; 95% CI (1.53-12.45); P=0.006]. Conclusions: The MAS-associated fatality rates in preterm infant was significantly high. Female, persistent pulmonary hypertension, and pulmonary hemorrhage were considered independent predictors of MAS-associated mortality.