Extended duration of clinical mastitis (CM) treatment has been advocated, although results showing its higher efficacy compared with standard treatment are difficult to compare and seem conflicting. In a non-blinded, positively controlled clinical trial with systematic allocation, the efficacy of a standard, 1·5-d cefquinome treatment (ST), and an extended, 5-d intramammary cefquinome treatment (ET) were evaluated. The latter is frequently performed in cows with persistent high somatic cell count (SCC), expecting a better cure. Therefore, cows with CM immediately preceded by at least two consecutive monthly elevated SCC >200 000 cells/ml, were studied. The primary efficacy criteria were bacteriological cure (BC) and clinical cure (CC), while SCC cure was considered a secondary criterion of cure. Least square means of overall BC were not different after ET (79%, n=206) compared with ST (72%, n=203). ET, as compared with ST, improved BC of CM when caused by streptococci, specifically Streptococcus uberis. At day 1·5, only 13% of quarters showed CC, increasing significantly towards 60% at day 5, and 99% at day 14 and at day 21. No significant difference in CC was present between treatment groups. Overall SCC cure was low (22%) and not significantly different between treatment groups, but significantly higher for cases due to enterobacteriacae compared with staphylococci. In conclusion, ET with cefquinome of CM in cows with a persistent high SCC seems to be only indicated when caused by streptococci, mainly Str. uberis but shows no advantage when no information on bacteriological causes of mastitis is available. In our data, absence of CC directly after ST was not related to eventual BC.