BACKGROUND: Glässer's disease, caused by Glaesserella parasuis (G. parasuis), is a widespread bacterial infection in swine that leads to significant economic losses. G. parasuis, a member of the normal microbiota within the Pasteurellaceae family, exhibits horizontal resistance gene exchange and intracellular invasion capabilities, increasing the risk of developing resistant isolates. Accurate antimicrobial therapy is essential for controlling Glässer's disease. The production systems for exotic crossbred pigs and Taiwan black pigs differ considerably. To inform Glässer disease control and monitor antimicrobial resistance, we assessed the antimicrobial susceptibilities of G. parasuis isolates, analyzed them using normalized resistance interpretation (NRI), and compared findings between the two production systems. RESULTS: A total of 154 G. parasuis isolates from 106 exotic crossbred pig herds and 48 Taiwan black pig herds were tested against 16 antimicrobial agents between 2015 and 2020. Due to the absence of specific breakpoints for G. parasuis, NRI was utilized to define non-wild-type (non-WT) populations based on minimum inhibitory concentration (MIC) distributions. Non-WT subpopulations of isolates for amoxicillin, ampicillin, ceftiofur, gentamicin, kanamycin, and tiamulin were observed. The highest MIC CONCLUSIONS: This study provides the susceptibility profile of G. parasuis isolates for both exotic crossbred pigs and Taiwan black pigs in Taiwan and highlights potential antimicrobial resistance for aminocyclitol, aminoglycosides, beta-lactams, lincosamides, macrolides, and pleuromulin. Ceftiofur, cephalothin, doxycycline, and florfenicol could be most suitable for treating early-stage Glässer's disease. Nonetheless, increased attention should be paid to the responsible use of antimicrobials in light of the growing threat of antimicrobial resistance.