Emamectin benzoate (an avermectin chemotherapeutant administered to fish as an in-feed treatment) has been used to treat infestations of sea lice Lepeophtheirus salmonis on farmed Atlantic salmon Salmo salar in the Bay of Fundy, New Brunswick, Canada, since 1999. This retrospective study examined the effectiveness of 114 emamectin benzoate treatment episodes from 2004 to 2008 across 54 farms. Study objectives were to establish whether changes in the effectiveness of emamectin benzoate were present for this period, examine factors associated with treatment outcome, and determine variables that influenced differences in L. salmonis abundance after treatment. The analysis was carried out in 2 parts: first, trends in treatment effectiveness and L. salmonis abundance were explored, and second, statistical modelling (linear and logistic regression) was used to examine the effects of multiple variables on post-treatment abundance and treatment outcome. Post-treatment sea lice abundance increased in the later years examined. Mean abundance differed between locations in the Bay of Fundy, and higher numbers were found at farms closer to the mainland and lower levels were found in the areas around Grand Manan Island. Treatment effectiveness varied by geographical region and decreased over time. There was an increased risk for unsuccessful treatments in 2008, and treatments applied during autumn months were more likely to be ineffective than those applied during summer months.