The aim of this study targeted the evaluation of the in vivo effect of moxifloxacin in the treatment of patients with severe odontogenic abscesses. This was a prospective, two-armed, randomised, unblinded, monocentric pilot study, which enrolled 21 hospitalized patients with severe odontogenic abscesses. After extraoral incision, patients were either treated with moxifloxacin 400 mg i.v. once daily or amoxicillin/clavulanic acid 2.2 g i.v. three times daily. Primary clinical endpoint was the time until clinical remission, represented by simultaneous assertion of the following criteria: body temperature <38.5 degrees C, no pain at palpation, and mouth opening similar or better than preoperatively. White blood cell count, C-reactive protein, pain, health related quality of life (HR-QoL) and length of hospital stay were recorded as secondary outcome criteria. The mean duration until reaching the primary end point was 6.6 (range, 4.3-8.8) days in the moxifloxacin group and 6.0 (range, 3.8-8.2) days in the amoxicillin/clavulanic acid group. Median days of in-house treatment ranged between five and six days for both groups. HR-QoL was highly impaired in both groups preoperatively and reached near normal on days three and four in both samples. In this pilot investigation, moxifloxacin showed promising results as compared to amoxicillin/clavulanic acid. Therefore, a larger prospective clinical trial using moxifloxacin in severe odontogenic abscesses appears encouraging. We suggest a combination of body temperature, palpatory pain, and subjective pain as a parameter for successful intervention; however, both findings need prospective validation by means of a phase III evaluation.