Climate forecasts predict an increase in frequency and intensity of wildfires. Associations between health outcomes and population exposure to smoke from Washington 2012 wildfires were compared using surface monitors, chemical-weather models, and a novel method blending three exposure information sources. The association between smoke particulate matter ≤2.5 μm in diameter (PM2.5) and cardiopulmonary hospital admissions occurring in Washington from 1 July to 31 October 2012 was evaluated using a time-stratified case-crossover design. Hospital admissions aggregated by ZIP code were linked with population-weighted daily average concentrations of smoke PM2.5 estimated using three distinct methods: a simulation with the Weather Research and Forecasting with Chemistry (WRF-Chem) model, a kriged interpolation of PM2.5 measurements from surface monitors, and a geographically weighted ridge regression (GWR) that blended inputs from WRF-Chem, satellite observations of aerosol optical depth, and kriged PM2.5. A 10 μg/m3 increase in GWR smoke PM2.5 was associated with an 8% increased risk in asthma-related hospital admissions (odds ratio (OR): 1.076, 95% confidence interval (CI): 1.019–1.136); other smoke estimation methods yielded similar results. However, point estimates for chronic obstructive pulmonary disease (COPD) differed by smoke PM2.5 exposure method: a 10 μg/m3 increase using GWR was significantly associated with increased risk of COPD (OR: 1.084, 95%CI: 1.026–1.145) and not significant using WRF-Chem (OR: 0.986, 95%CI: 0.931–1.045). The magnitude (OR) and uncertainty (95%CI) of associations between smoke PM2.5 and hospital admissions were dependent on estimation method used and outcome evaluated. Choice of smoke exposure estimation method used can impact the overall conclusion of the study.