While the impact of absolute extreme temperatures on human health has been amply studied, far less attention has been given to relative temperature extremes, that is, events that are highly unusual for the time of year but not necessarily extreme relative to a location’s overall climate. In this research, we use a recently defined extreme temperature event metric to define absolute extreme heat events (EHE) and extreme cold events (ECE) using absolute thresholds, and relative extreme heat events (REHE) and relative extreme cold events (RECE) using relative thresholds. All-cause mortality outcomes using a distributed lag nonlinear model are evaluated for the largest 51 metropolitan areas in the US for the period 1975–2010. Both the immediate impacts and the cumulative 20-day impacts are assessed for each of the extreme temperature event types. The 51 metropolitan areas were then grouped into 8 regions for meta-analysis. For heat events, the greatest mortality increases occur with a 0-day lag, with the subsequent days showing below-expected mortality (harvesting) that decreases the overall cumulative impact. For EHE, increases in mortality are still statistically significant when examined over 20 days. For REHE, it appears as though the day-0 increase in mortality is short-term displacement. For cold events, both relative and absolute, there is little mortality increase on day 0, but the impacts increase on subsequent days. Cumulative impacts are statistically significant at more than half of the stations for both ECE and RECE. The response to absolute ECE is strongest, but is also significant when using RECE across several southern locations, suggesting that there may be a lack of acclimatization, increasing mortality in relative cold events both early and late in winter.