The regeneration ecology of sugar maple (Acer saccharum Marsh.) has been impacted by acid rain leaching of base cations from the soils throughout much of its range. We tracked the survival and causes of death for a natural cohort of sugar maple seedlings across 22 sites in the Hubbard Brook Valley in New Hampshire, USA, where soil acidification has been documented. Survival over 7 years averaged 3.4%; however, significant differences in survival were observed among sites, which were classified into three main groups based on the shape of their survival curves. These site groups differed in position on the landscape, seedling nutrition and leaf size, and the prevalence of damage agents, but not in soil Ca. First-season mortality was high (71%), and the main damage agents were fungal infection (Rhizoctonia spp.) and caterpillar herbivory (Geometridae). Other principal causes of mortality in order of importance were winter injury, mechanical damage, and rodent (Myodes gapperi Vigors, 1830) tunneling, and all damage agents varied significantly in severity between years. This study highlights the importance of landscape-level variation in biotic factors for predicting sugar maple regeneration success. Predictions of sugar maple regeneration will require a better understanding of controls on initial seedling growth and the suite of biotic agents that damages seedlings.