A non-blinded, positively controlled trial was conducted to evaluate the efficacy of an alternative, non-antibiotic therapy with Pyrogenium® to reduce ineffective antibiotic usage in the treatment of non-severe clinical mastitis (CM) in cows with longer lasting udder diseases. The solely treatment with Pyrogenium® (6 times, at a 12 hourly interval and then 4 times in a 24-hour interval) were compared with the reference treatment of solely local antibiotic therapy. The matched field study was conducted on five free-stall dairy farms located in Northern Germany. Cases of mild-to-moderate CM in cows with longer lasting high somatic cell counts in preceding dairy herd improvement test days and with previous CM cases in current lactation (chronic mastitis) were randomly allocated to one of the two treatment groups. A foremilk sample of the affected quarter was taken before treatment and again approximately 7 days, 14 days and 21 days after the end of therapy for cyto-bacteriological examination. Primary outcome was clinical cure (CC). Bacteriological cure (BC), quarter somatic cell count cure (CYC) and CM recurrence within 60 days after the end of treatment were chosen as secondary outcomes although low probabilities of bacteriological cure and quarter somatic cell count cure for selected cows were expected. The study resulted in the following findings: the pathogens mostly cultured from pretreatment samples were Staphylococcus aureus, followed by Streptococcus uberis. There were no significant differences between the test treatment (EG) in comparison with the reference treatment (CG) regarding all outcome variables (e.g. CC: EG 60.0%, CG 54.7%). Having regard to the selection criteria of cows in this study, the findings indicated that sole treatment with Pyrogenium® in non-severe CM cases may constitute an alternative therapy to reduce antibiotics.