Multilevel random intercept logistic and Poisson regression were used to model associations between various antimicrobial use practices and resistance to individual and multiple antimicrobials among generic fecal Escherichia coli isolated from Alberta finishing swine. In-feed antimicrobial use in finishers was significantly associated with increased risk of resistance to ampicillin, chloramphenicol, streptomycin, and sulfisoxazole in generic E. coli isolates. Chlortetracycline use in grower rations was associated with ampicillin and tetracycline resistance. Use of in-feed antimicrobials in finishers was significantly associated with increased risk of resistance of generic E. coli to multiple antimicrobials. The study findings suggest that certain farm-level interventions related to antimicrobial use might be beneficial in reducing development and emergence of antimicrobial resistance in swine populations.