Abstract: OBJECTIVE To explore the association of plasma caspofungi (CAS) concentrations with adverse reactions of critically ill patients in ICU and identify the threshold value of trough concentration (Cmin) in prediction of reversible thrombocytopenia. METHODS A total of 81 adult patients who received CAS antifungal therapy and completed plasma concentration surveillance in the ICU of Hainan Provincial People's Hospital from Jan. 2021 to Dec. 2024 were retrospectively enrolled in the study and were divided into the adverse reaction group with 34 cases and the no adverse reaction group with 47 cases according to the status of adverse reactions during the treatment period. The data were collected from the subjects, including general demographic data, underlying diseases, hepatorenal function indexes, peak concentration of CAS (Cmax) and Cmin. The incidence of adverse reactions was evaluated based on predefined criteria. Multivariate logistic regression analysis was performed for risk factors for the adverse reactions, and the efficiency of CAS Cmin in prediction of reversible thrombocytopenia was assessed by ROC curves. RESULTS Among the 81 patients, 34 (41.98%) had adverse reactions; the CAS Cmin of the adverse reaction group was higher than that of the no adverse reaction group(P=0.023). Multivariate logistic regression analysis showed that the CAS Cmin was the risk factors for the adverse reactions(OR=1.324,95%CI:1.010 to 1.736,P=0.042). ROC curve analysis indicated that the AUC of the CAS Cmin was 0.883 in prediction of reversible thrombocytopenia, with the optimal cutoff value 7.32 μg/ml. CONCLUSIONS The high Cmin of CAS of critically ill ICU patients is associated with the increase of risk for adverse reactions. The risk for reversible thrombocytopenia increases remarkably when Cmin is ≥7.32 μg/ml. It is necessary to strengthen the plasma concentration surveillance and optimize the individualized drug dosing regimen.