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Inappropriate antimicrobial therapy for surgical site infections (SSIs) can lead to poor outcomes and an increased risk of antibiotic resistance. A nationwide survey was conducted in Japan from 2021 to 2023 to investigate the antimicrobial susceptibility of pathogens isolated from SSIs. The data were compared with those obtained in the 2010, 2014-2015, and 2018-2019 surveillance studies. The rate of detection of extended-spectrum β-lactamase-producing strains of Enterobacterales was 4.4% in 2010, 13.5% in 2014-2015, and 6.6% in 2018-2019, the incidence increased to 11.2% in 2021-2023. A high rate of susceptibility to tazobactam/piperacillin was detected in the 2018-2019 survey, and this decreased to 71.8% in the 2021-2023 survey. The geometric mean MICs for tazobactam/ceftolozane showed an increasing trend (0.397 in 2018-2019 and 0.778 in 2021-2023). The MRSA incidence rate decreased from 72% in the first surveillance to 53% in the second and third surveillance and to 39% in the fourth surveillance. The susceptibility of E. coli and K. pneumoniae to sulbactam/ampicillin and cefazolin decreased. For Bacteroides species, low levels of susceptibility were observed for moxifloxacin (57%), cefmetazole (54%), and clindamycin (44%). In conclusion, antimicrobial susceptibility changed mainly for Enterobacterales isolated from SSIs. Bacterial sensitivity to carbapenems was generally good, suggesting that the use of antimicrobial agents may have contributed to the observed reduction in MRSA incidence.