A replicated field study was conducted during the grazing season (May to October) for 5 consecutive years (2006 to 2010) on pastures naturally infected with gastrointestinal nematodes in South East Scotland to compare the impact of four ivermectin treatment regimes on drug efficacy and lamb body weight. The four regimes were: neo-suppressive treatment of all lambs every 4 weeks (NST), performance based targeted selective treatment (TST) regime (implementing the Happy Factor™, TST), strategic prophylactic treatment (SPT) where all lambs were treated at strategically appropriate times, at weaning and 6 weeks post-weaning and finally, a metaphylactic/therapeutic treatment (MT) where all lambs were treated when some individuals exhibited clinical signs of parasitism e.g high faecal egg count (FEC), scouring and/or weight loss. Body weights and FEC were determined fortnightly for all lambs. Ivermectin efficacy was assessed using individual FEC from days 0 and 14 post treatment. The mean numbers of ivermectin drenches administered per grazing season were 4.0, 1.8, 2.0 and 1.4 for the NST, TST, SPT and MT groups, respectively. The mean efficacy (95% lower and upper confidence limits) in the NST group declined from 95.1% (93.3%, 96.8%) in 2006 to 61.7% (55.4%, 67.8%) in 2010, whereas the mean efficacy in other treatment groups in 2010 were 86.4% (80.7%, 91.5%), 86.2% (82.5%, 89.9%), and 82.9% (77.9%, 87.6%) for the TST, SPT and MT groups, respectively. The TST approach provided the greatest maintenance of drug efficacy overall, with a maximum decline in mean efficacy of 9.0%, whereas maximum declines in other groups were 33.4, 11.6 and 14.4% for the NST, SPT and MT, respectively. Compared with the NST group, there was no evidence that the reduction in the number of anthelmintic treatments administered affected the mean bodyweight at day 154 in the TST or SPT lambs (p >0.05) across all years. However, in the first 3 years mean body weight in the MT group was significantly lower than that of the NST group (p ≤ 0.04). This suggests that both the TST and SPT anthelmintic regimes can maintain both body weight and drug efficacy despite reductions in anthelmintic use. This study provides the first in situ evidence that the frequency of treatment and the proportion of the population treated affect the rate of change of efficacy of ivermectin treatment, when considering lamb only treatments. The use of TST to identify animals that are less reliant on anthelmintic could be an additional benefit of this approach.