The objective of these investigations was to evaluate efficacy of recommended and extended therapy with pirlimycin hydrochloride (Pirsue, Pharmacia/Upjohn Co.) for gram positive subclinical intramammary infections in 4 high SCC herds. Cow and quarter S. aureus cure rates ranged from 0–10, and 3–50%, respectively. Variation in cure rates across herds was attributed to differences in initial herd prevalence and herd management, treatment regime, and willingness to make necessary herd management changes. Bacterial cure rates were overestimated at 12 days post treatment. SCC at day 12 post treatment was a better indicator of cure than bacterial culture. This supports that bacterial cure should be assessed at least 21–28 days post treatment. This also supports the use of extended therapies depending on organism involved and chronicity of infection, and that therapy success hinges on herd management practices and attitudes.