Atmospheric nitrogen (N) fixation by Alnus tenuifolia can account for up to 70% of the N accumulated during vegetation development along river floodplains in interior Alaska. We assessed disease incidence and related mortality of a recent outbreak of fungal stem cankers on A. tenuifolia across three regions in Alaska during the 2005 growing season, and determined the impacts on N-fixation rates, nodule biomass, and stand-level N-fixation inputs. The highest percentage of ramets colonized or dead with canker was found on Tanana River plots, suggesting the epidemic is most severe in the Fairbanks region. A positive relationship between % basal area loss to canker and % canopy loss provides a simple means for assessing stand-level mortality associated with disease in the field. Although specific N-fixation (SNF) rates were not influenced by canker disease incidence of individual genets, live nodule biomass beneath alder canopies was inversely correlated with the percentage of ramets dead or with main ramet canker. Variations in SNF and live nodule biomass translated to differences in N-fixation inputs, which ranged from 22 to 107 kg N ha−1 y−1 across study regions. Nodule biomass was reduced by incidence of canker disease and related mortality an average of 24% across all sites, which translates to N input reductions of 8, 16, and 33 kg N ha−1 y−1 for the three regions, respectively. During the 2008 growing season, we resurveyed the Tanana River plots and found that of the ramets larger than 4-cm diameter having main ramet canker in 2005, 74% are now dead; and for those without main ramet canker in 2005, 25% have developed main ramet canker, and 8% are dead. Thus, it is likely that N-fixation inputs have declined further below what we estimated for 2005.