In a controlled and randomized field trial carried out in three European countries, 219 fattening pigs, from seven farms with respiratory disease problems, were treated intramuscularly for three or five days either with marbofloxacin 2 mg/kg/day, or with amoxicillin 7 mg/kg/day. Pigs were monitored daily until D5 (Day 5) and again at D21, and were weighed at D0 and D21.Pasteurella multocida,Actinobacillus pleuropneumoniae, andMycoplasma hyopneumoniaewere mainly identified in the pig lungs. The difference in the cure rate (74.5% in marbofloxacin groupversus68% in the amoxicillin group) was not significant. Mean rectal temperature was significantly lower after treatment with marbofloxacin. Other criteria tended to be favourable for the marbofloxacin group, although differences were not significant. The time to cure tended to be shorter for the marbofloxacin group (24.3% of pigs at 24 hours post‐treatmentversus12.1% in the amoxicillin group). Marbofloxacin and amoxicillin relapse rates were 11.9% and 17.2% respectively (not significant) and daily weight gain was 746 g in the marbofloxacin groupversus687 g in the amoxicillin group (not significant). The 2% marbofloxacin solution was significantly better tolerated than amoxicillin.