In primary care, urinary tract infections (UTIs) account for the majority of antibiotic prescriptions. Comments from microbiologists on interpreting the antimicrobial susceptibility testing (AST) profile for urinalysis were made to improve the prescription of antibiotics. We aimed to explore the added value of these comments on the quality of antibiotic prescribing by a superior double-blind digital randomized case-vignette trial among French general practitioners (GPs). One case vignette with (intervention) or without (control) a ‘comment’ after AST was randomly assigned to GPs. Among 815 participating GPs, 64.7% were women, at an average age of 37 years. Most (90.1%) used a computerized decision support system for prescribing antibiotics. Empirical antibiotic therapy was appropriate in 71.9% (95% CI, 68.8–75.0) of the cases, without differences between arms. The overall appropriateness of targeted antibiotic therapy (primary outcome) was not significantly increased when providing ‘comments’: 83.4% vs. 79.9% (OR = 1.26, 95% CI, 0.86–1.85). With the multivariate analysis, the appropriateness was improved by 2-folds (OR = 2.38, 95% CI, 1.02–6.16) among physicians working in healthcare facilities. Among digital-affine young general practitioners, the adjunction of a ‘comment’ by a microbiologist to interpret urinalysis in community-acquired UTIs did not improve the overall level of appropriateness of the targeted antibiotic.