Infusion of a long-acting antibiotic preparation at drying off in dairy cows as a prophylactic therapy is usually recommended for all quarters where it is in use. Studying the effectiveness of such treatment using quarter as the unit of analysis assumes that each quarter within a cow has a risk of being infected independent of the other quarters of the cow. Failure to account for interdependence of quarters within a cow may lead to inaccurate variance estimates and errors in assessing treatment effects. Data from two trials assessing different dry-cow strategies were examined for interdependence of infection between quarters. Logistic regression with a variance inflation factor or a multilevel analysis was used to assess the effect of antibiotic and internal teat-sealant dry cow strategies. Parity and infection status at drying off were covariates in the analysis. Interdependence of the risk of quarter infections within control-group cows was demonstrated in both dry-cow antibiotic and teat-seal trials. However, cows that received either of these treatments did not demonstrate interdependence. Treated quarters in both trials were 3.0 times less likely to acquire a new infection at calving compared with the untreated controls. Quarters in cows of parity 3 or greater were also at an increased risk in the antibiotic treatment trial. In both trials, quarters with either Corynebacterium spp. or coagulase-negative staphylococci infections at drying off had an increased risk of a new intramammary infection at calving. This study has demonstrated the beneficial and comparable effects of antibiotic and teat seal dry cow strategies; both decreased the risk of intramammary infection at calving. The application of dry-cow strategies at the cow level and not the quarter level is also supported.