OBJECTIVE： To compare the methods of LC-MS/MS and MEIA for the determination of digoxin concentrations in human plasma. METHODS： The concentration of digoxin in standard controls and samples from 50 patients were respectively determined by LC-MS/MS and MEIA methods， and the results obtained by the two methods were analyzed using paired t test. RESULTS： There was no statistical difference between the data of standard controls by LC-MS/MS and MEIA methods （P＞0.05）. However， the results of 50 samples from patients showed that MEIA data were significantly higher than LC-MS/MS data， there was statistically significant difference （P＜0.01）. CONCLUSIONS： There is considerable variation between MEIA data and practical data. Compared with the MEIA， LC-MS/MS is more suitable for clinical determination of digoxin plasma concentration.