Nadifloxacin has good activity against Propionibacterium acnes as well as against both meticillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) and Staphylococcus epidermidis. The aim of this study was to evaluate the activity of this fluoroquinolone against the abovementioned microorganisms, comparing isolates collected in 2007 in Germany, a country where nadifloxacin has been used for the last 2 years, with isolates collected from 2006-2007 in Spain where nadifloxacin has not been used. A collection of P. acnes from Hungary (strains collected during 2005-2006) and a collection of P. acnes from different countries in Europe (collected during 2002) were also included. The activity of nadifloxacin was compared with ciprofloxacin, erythromycin and clindamycin. Susceptibility testing of P. acnes was performed by agar dilution, whereas the susceptibility of the different staphylococci was determined by microdilution. Although the isolates were collected from three different countries (Spain, Hungary and Germany) where the use of quinolones can produce a different effect, no significant differences in the percentages of resistance to nadifloxacin were observed in P. acnes, MSSA, MRSA and S. epidermidis. Therefore, topical antibiotics such as nadifloxacin do not have an additional effect on resistance. Moreover, nadifloxacin presented much better activity than the comparator drugs used in this study against the studied microorganisms.