A practical method to prepare 7-amino-3-(substituted thiomethyl)-3-cephem-4-carboxylic acids (1) was developed. The acetoxy group of 3-acetoxymethyl-7-amino-3-cephem-4-carboxylic acid (7-ACA, 2) was displaced by various thiols in the presence of strong acids (including Lewis acids) under nonaqueous conditions to afford 1 in high yields. Similar substitution of the Δ²-isomers of 2 was achieved by the same method.