Blastomycosis is a potentially fatal fungal infection endemic to parts of North America. We used national multiple-cause-of-death data and census population estimates for 1990-2010 to calculate age-adjusted mortality rates and rate ratios (RRs). We modeled trends over time using Poisson regression. Death occurred more often among older persons (RR 2.11, 95% confidence limit [CL] 1.76, 2.53 for those 75-84 years of age vs. 55-64 years), men (RR 2.43, 95% CL 2.19, 2.70), Native Americans (RR 4.13, 95% CL 3.86, 4.42 vs. whites), and blacks (RR 1.86, 95% CL 1.73, 2.01 vs. whites), in notably younger persons of Asian origin (mean = 41.6 years vs. 64.2 years for whites); and in the South (RR 18.15, 95% CL 11.63, 28.34 vs. West) and Midwest (RR 23.10, 95% CL14.78, 36.12 vs. West). In regions where blastomycosis is endemic, we recommend that the diagnosis be considered in patients with pulmonary disease and that it be a reportable disease.