〔Abstract〕 Objective To investigate the diagnostic value of plasma calprotectin in childern with refractory mycoplasma pneumoniae pneumonia(RMPP). Methods A multicenter, prospective cohort study was conducted, enrolling 228 children with mycoplasma pneumoniae pneumonia(MPP). Among these, 177 cases were diagnosed with general mycoplasma pneumoniae pneumonia(GMPP), while the remaining 51 cases were RMPP. Plasma was collected at the time of admission of the children in both groups, and calprotectin levels were measured. A one-way difference analysis was performed on the blood test indexes of the children in the two groups, and the difference variables withP<0.05 between the two groups were included in a multifactorial logistic regression to analyze the risk factors for the progression of GMPP to RMPP. The differential diagnostic value of plasma calprotectin for GMPP and RMPP was analyzed by the receiver operating characteristic(ROC) curves. Results Univariate analysis showed that plasma calprotectin levels were significantly higher in the RMPP group than those in the GMPP group, and the difference was statistically significant(P<0.05). Logistic regression analysis showed that plasma calprotectin was an independent risk factor for RMPP(OR=1.323,P<0.001), ROC curve analysis showed that plasma calprotectin had a higher diagnostic value for the differential diagnosis of GMPP and RMPP(AUC =0.839), and its combination with C-reactive protein and albumin could significantly improve the diagnostic efficiency. Conclusion Plasma calprotectin has good clinical value for the diagnosis of RMPP.