This study compared the effect of sodium dodecyl-sulfate, potassium ferricyanide, and preincubation technique to continuous-flow analysis and prior deproteinization to correct the negative interference of bilirubin on serum creatinine found by the kinetic Jaffé reaction. Bilirubin increased to 684 mumol/L did not interfere with serum creatinine measured by the methods incorporated with dialysis or deproteinization. Trichloroacetic acid was the best protein precipitant. The reagent incorporated with sodium dodecyl sulfate was more appropriate to minimize bilirubin interference than reagent containing potassium ferricyanide. An increase in potassium ferricyanide concentration resulted in false positive creatinine values. Incorporation of both SDS and potassium ferricyanide in the reagent did not help in minimizing the bilirubin interference over use of each chemical alone. The 10 minutes of preincubation of the sample with alkaline buffer incorporating with either SDS or potassium ferricyanide before starting the Jaffé reaction was the appropriate way to overcome unconjugated bilirubin interference at a level of 342.0 mumol/L. However, the technique did not work uniformly with icteric patient sera containing conjugated, unconjugated, and delta bilirubin. This is a challenging problem that remains to be solved by the clinical chemist.