Antibiotic resistance of Brachyspira hyodysenteriae, especially to pleuromutilins, is a matter of concern in several countries. In the present study, the antimicrobial susceptibilities of 30 Belgian B. hyodysenteriae isolates from 24 swine herds were tested and compared with the clinical effect of treatment. In vitro, no resistance to tiamulin was found, but two isolates(6%) were classified as intermediately susceptible. All isolates were susceptible to valnemulin at low concentrations (MIC50: ≤0.03 µg/ml). Higher minimal inhibitory concentrations (MICs) for valnemulin were found in isolates with higher MICs for tiamulin. For lincomycin, 16 (53%) isolates were classified as resistant and 4 (13%) isolates as susceptible. For tylosin, a high percentage of resistance(96%) was recorded. The MICs for 50% of the strains for salinomycin and doxycycline were 0.5 and 4 µg/ml, respectively. Subsequently, the in vitro data obtained were compared with the farm history and clinical efficacies in 23 of the 24 swine herds of origin as judged by the attending veterinarians. The effect of treatment as evaluated in the field was generally in agreement with the in vitro data for these antibiotics. However, a clinical interpretation of certain breakpoints is imperative. A revision of the clinical breakpoint for tiamulin is proposed. Isolates with MIC ≥1µg/ml should be considered as not responding to therapy in vivo. Consequently, the therapeutic use of another compound is indicated. In the third part of this study, the in vitro MIC for lincomycin was compared in detail with the effect of treatment on four farms. Even though in vitro all isolates were classified as resistant, a good response to treatment was observed on two farms. On one of these farms, however, the disease reappeared after treatment was discontinued. It was concluded that in vitro susceptibility testing of B. hyodysenteriae for lincomycin only partially predicted clinical effect of treatment in the field.