Background: Newer analytical methods are introduced in clinical biochemistry laboratory for the purpose of improvement of quality, automation, to reduce the cost or to simply measure a new analyte. Serum creatinine is one of the renal function test. Creatinine is measured in serum by modified Jaffé’s method which involves wet chemistry (SCrMJ) and the new dry chemistry which utilizes the microslides and involves enzymes (SCrMS). Various kits available commercially which are based on enzymatic methods to overcome the shortcomings and problems inherent in the Jaffé’s method. Aim: The aim of the present study is to compare the results of creatinine estimation by modified Jaffé’s method (SCrMJ) or wet chemistry and dry chemistry (SCrMS) in icteric and haemolytic serum samples. Methods and Materials: Forty serum samples each of icterus and haemolysis were analyzed by modified Jaffé’s method (SCrMJ) (wet method) and patented dry chemistry (SCrMS) method developed by ortho clinical diagnostics. Results: The Creatinine concentration in serum is comparatively lower when estimated by dry chemistry (SCrMS) developed by ortho clinical diagnostics on Vitros 250 analyzer as compared to modified Jaffé’s method (wet chemistry). The values of creatinine are found to be both accurate and precise by the enzymatic method in icteric and haemolytic serum samples. Conclusions: Dry chemistry eliminates the possibility of overestimation of creatinine in icteric and haemolytic samples and estimate the true value of creatinine in serum for better treatment planning.