We estimated cardiopulmonary morbidity and mortality associated with wildfire smoke (WFS) fine particulate matter (PM2.5) in the Front Range of Colorado from 2010 - 2015. To estimate WFS PM2.5, we developed a daily kriged PM2.5 surface at a 15km X 15km resolution based on the Environmental Protection Agency Air Quality System monitors for the western United States; we subtracted out local seasonal‐average PM2.5 of non‐smoky days, identified using satellite‐based smoke plume estimates, from the local daily estimated PM2.5 if smoke was identified by National Oceanic and Atmospheric Administration’s Hazard Mapping System. We implemented time‐stratified case‐crossover analyses to estimate the effect of a 10 µg/m3 increase in WFS PM2.5 with cardiopulmonary hospitalizations and deaths using single and distributed lag models for lags 0 - 5 and distinct annual impacts based on local and long‐range smoke during 2012, and long‐range transport of smoke in 2015. A 10 µg/m3 increase in WFS was associated with all respiratory, asthma, and chronic obstructive pulmonary disease hospitalizations for lag day 3 and hospitalizations for ischemic heart disease at lag days 2 and 3. Cardiac arrest deaths were associated with WFS PM2.5 at lag day 0. For 2012 local wildfires, asthma hospitalizations had an inverse association with WFS PM2.5 (OR: 0.716, 95% CI: 0.517 - 0.993), but a positive association with WFS PM2.5 during the 2015 long‐range transport event (OR: 1.455, 95% CI: 1.093 - 1.939). Cardiovascular mortality was associated with the 2012 long‐range transport event (OR: 1.478, 95% CI: 1.124, 1.944).