The present study demonstrates successful herd sanitation and eradication of contagious mastitis caused by Staphylococcus aureus genotype B (GTB) in an entire Swiss district (Ticino) including 3,364 dairy cows from 168 farms. Herd sanitation included testing of all cows using a highly GTB-specific and sensitive real-time quantitative PCR (qPCR) assay, implementation of related on-farm measures, appropriate antibiotic therapy of GTB-positive cows, and culling of therapy-resistant animals, respectively. A treatment index was used as an objective criterion to select GTB-positive cows eligible for culling and replacement payment. Sixty-two herds (37%) were initially GTB-positive with a cow prevalence between 10% and 100% and were submitted to sanitation. Twenty months after the start of the campaign, all of these herds were free from S. aureus GTB, whereby 73% of them were sanitized during the first 7 mo. At the cow level, a total of 343 animals were infected. Fifty of them were immediately culled and farmers were financially compensated based on their treatment index value. The remaining 293 cows were intramammarily treated with antibiotics either during lactation using the combination of cephalexin-kanamycin or penicillin gentamicin or at dry-off using cloxacillin. Out of these cows, 275 (93.9%) were treated successfully, meaning that their milk was twice GTB-negative by qPCR after therapy. For lactational treatment, control samples were taken ≥10 and ≥20 d after treatment, for dry-off treatment ≥14 and ≥24 d after parturition. Neither lactation number nor SCC before treatment of the cow nor the type of therapy was associated with therapeutic cure. Using data of 30 GTB-positive and 71 GTB-negative herds (1,855 observations), the effect of GTB sanitation on bulk tank milk SCC (BTSCC) was evaluated by applying a linear mixed statistical model. In the year before sanitation, BTSCC was always higher in GTB-positive than in GTB-negative herds. After the start of the campaign, BTSCC declined rapidly in the herds under GTB sanitation and achieved values that no longer differed statistically from those of GTB-free herds after only 2 mo, remaining very similar for the rest of the campaign. The farmers were very satisfied with the outcome of the campaign because all GTB-positive herds could be sanitized rapidly, sanitation was sustainable, and milk quality increased.