The effect of tilmicosin on the incidence of clinical mastitis and subsequent lamb performance was studied in 9 sheep flocks in Ontario. Ewes were treated randomly with either tilmicosin or placebo approximately one month prior to lambing. Outcome was assessed by comparing rates of clinical mastitis, palpable udder abnormalities, and preweaning (50-day) lamb weights between the 2 treatment groups, while controlling for other important variables. Lambs raised by multiparous ewes treated with tilmicosin were significantly heavier than lambs from placebo-treated multiparous ewes at 50 days. Lambs from tilmicosin-treated ewes were on average 0.52 kg heavier than lambs in the placebo group. There was no difference between treatment groups in the weight of lambs from first parity ewes. Tilmicosin treatment resulted in a 43% decrease in palpable udder abnormalities. Incidence of clinical mastitis did not differ between experimental groups. The administration of tilmicosin prelambing, at the time of routine clostridial disease vaccination, may be a beneficial and convenient way to reduce mastitis infection and improve the preweaning gain of lambs.