In this article, fomepizole was prepared from isobutyraldehyde or 2-methyl-2-propenal in three ways. Both of the starting materials were reacted with 80% hydrazine hydrate (w%), sulfuric acid and potassium iodide. By exploring the influence of adding order, concentration and reaction temperature on the yield, optimize the process. The first process started with isobutyraldehyde, with low boiling point. It was convenient by changing the way of feeding, which can avoid using of autoclave, and the yield was 40%. The second process had been changed to use 2-methyl-2-propenal, avoiding weakness of low boiling point. By optimizing the reaction conditions, the yield can reach to 80%. The third one showed complex operation, with the usage of hydrogen peroxide, which was not suitable for industry. Conclusion: Among those three, the second one, which was operated simply with high yield, was most suitable for industry.