Shigella sonnei replaced Shigella flexneri to become the predominant species for shigellosis in 2001 to 2003 in central Taiwan. A total of 425 S. sonnei isolates collected from 1996 to 2004 were available for characterization by pulsed-field gel electrophoresis (PFGE), inter-IS1 spacer typing (IST), and antimicrobial susceptibility testing. The results showed that at least 21 IST clones had emerged for the S. sonnei infections in 1996 to 2004. Most IST clones lasted for a short time; some circulated for 2 to 3 years. An IST1 clone, detected for the first time in 2000, was the most prevalent and responsible for the shigellosis epidemic in 2001 to 2003. Over 3 years of sustained transmission, the IST1 clone evolved into many strains with different PFGE genotypes and antibiograms. The ancestor, with a J16N09.0019 PFGE genotype, remained to be the predominant circulating strain in the period studied; however, new strains with certain PFGE genotypes and antibiograms could become major circulating strains for subsequent infections.