Second-order calibration and multivariate spectroscopic-kinetic measurements in the visible region are proposed to improve the Jaffe method for creatinine assay. Analyses performed on synthetic mixtures containing bilirubin, glucose, and albumin confirm that second-order calibration is useful for creatinine determination in human serum. Quantitative determinations of creatinine with the parallel factor analysis (PARAFAC) and direct trilinear decomposition (TLD) methods were compared. It is shown that both methods can be used for creatinine determination in human serum, with an SEP (squared error of prediction) of 2.22 and coefficient of variability of 6.14% for PARAFAC, and an SEP of 2.38 and coefficient of variability of 6.57 % for TLD.5815460