by Ruwini Rupasinghe, Brittany L. Morgan Bustamante, Rebecca C. Robbins, Maria J. Clavijo, Beatriz Martínez-LópezMultidrug resistance (MDR) is frequently evident in Streptococcus suis, generating distinct antimicrobial resistance (AMR) profiles, which limits the effective antimicrobial drug (AMD) options against S. suis in pigs and humans. Despite its significance, there is a lack of studies and pertinent methodologies that uncover complex interactions among AMDs and associated resistance patterns. This study aimed to identify associations between phenotypic resistance patterns of S. suis isolates from swine production systems in the United States against common AMDs using Bayesian network analysis (BNA). Data from 259 unique S. suis isolates collected from 91 farms were included. Phenotypic susceptibility interpretations (resistance vs susceptible) of minimum inhibitory concentrations (MICs) were evaluated for 13 commonly used AMDs: ceftiofur (CEF), penicillin (PEN), enrofloxacin (ENR), gentamicin (GEN), neomycin (NEO), spectinomycin (SPC), sulfadimethoxine (SUL), tiamulin (TIA), tilmicosin (TIL), clindamycin (CLN), chlortetracycline (CHL), oxytetracycline (OXY), and tetracycline (TET). BNA was conducted using the R package bnlearn to identify joint resistance patterns and estimate conditional dependencies among resistance outcomes. Results revealed a high prevalence of MDR: 248 isolates (95.6%) were resistant to more than one AMD, and 209 isolates (80.7%) were resistant to at least one AMD in three or more classes. The Bayesian network comprised of 11 edges connecting 13 AMD nodes, highlighting statistical dependencies between AMDs resistances. PEN, TIA, and TIL were the most central nodes, with PEN connected to SUL, TIA, GEN, and CEF; TIA to PEN, SPC, TIL, and CLN; and TIL to SUL, TIA, CLN, and OXY. Other associations included CEF–SPC, TET–CLN, CEF–ENR, and OXY–CHL. These relationships implicate systematic dependencies between AMDs and may have resulted from mechanisms like cross-resistance and co-resistance. While these relationships are statistically derived and hypothesis-generating, they underscore the importance of understanding AMR patterns in guiding more effective AMD use. This approach can help prevent overuse, reduce treatment failures, and support AMR mitigation efforts for improved animal and public health outcomes.