ABSTRACT: Antimicrobial stewardship is a cornerstone of efforts to curtail antimicrobial resistance. To determine factors potentially influencing likelihood of prescribing antimicrobials for animals, we analyzed electronic health records for unwell dogs (n = 155,732 unique dogs, 281,543 consultations) and cats (n = 69,236 unique cats, 111,139 consultations) voluntarily contributed by 173 UK veterinary practices. Using multivariable mixed effects logistic regression, we found that factors associated with decreased odds of systemic antimicrobial prescription were client decisions focused on preventive health: vaccination (dogs, odds ratio [OR] 0.93, 95% CI, 0.90-0.95; cats, OR 0.92, 95% CI 0.89-0.95), insurance (dogs, OR 0.87, 95% CI 0.84-0.90; cats, OR 0.82, 95% CI 0.79-0.86), neutering of dogs (OR 0.90, 95% CI 0.88-0.92), and practices accredited by the Royal College of Veterinary Surgeons (OR 0.79, 95% 95% CI 0.68-0.92). This large multicenter companion animal study demonstrates the potential of preventive healthcare and client engagement to encourage responsible antimicrobial drug use.