Purpose: Elizabethkingia anophelis (E. anophelis) is an important extensively drug-resistant (XDR) pathogen to which there are limited therapeutic options. E. anophelis is perpetually misidentified as Elizabethkingia meningoseptica (E. meningoseptica) by conventional methods. Consequently, this study reassessed risk factors for infection and mortality, antimicrobial susceptibility patterns and carbapenem resistance mechanisms of E. anophelis.Methods: This retrospective case–control study was conducted to reveal the risk factors associated with E. anophelis infection and in-hospital mortality from 2015–2019 in a university tertiary hospital in southwest China using univariable and multivariable logistic-regression analysis. Case patients infected with E. anophelis isolates and controls patients with non-E. anophelis infections were compared at a ratio of 1:3 during the same time period. We employed the broth microdilution method to investigate the antimicrobial susceptibility profiles of 39 E. anophelis strains. PCR amplification, DNA sequencing and gene cloning were used to investigate the mechanisms of carbapenem resistance in E. anophelis.Results: We collected 39 non-repetitive E. anophelis isolates over the study period. Multivariate analysis indicated that coronary artery disease, chronic obstructive pulmonary disease, surgery in the past 6 months, anemia and systemic steroid use were independent risk factors for the acquisition of E. anophelis. Additionally, anemia was the only independent risk factor associated with in-hospital mortality in patients with E. anophelis infections. E. anophelis isolates showed high in-vitro susceptibility towards minocycline (100%) and piperacillin/tazobactam (71.8%), but were resistant to colistin, fosfomycin, ceftazidime/avibactam and aztreonam/avibactam. Additionally, we show that two metallo-β-lactamases (MBLs) BlaB and GOB, are responsible for carbapenem resistance and the serine-β-lactamase, CME, is functionally involved in resistance to cephalosporins and monobactams. Importantly, the various putative efflux pumps in E. anophelis are not responsible for resistance. Conclusion: Our findings will help clinicians identify high-risk patients and suggest that minocycline should be considered as an antibiotic therapeutic option for infections caused by E. anophelis. Additionally, carbapenem resistance in E. anophelis isolates is mainly associated with the MBLs, BlaB and GOB.