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Background: Epidemiologic studies have reported associations between fine particles (aerodynamic diameter ≤ 2.5 µm; PM_2.5) and mortality. However, concerns have been raised regarding the sensitivity of the results to model specifications, lower exposures, and averaging time.

Objective: We addressed these issues using 11 additional years of follow-up of the Harvard Six Cities study, incorporating recent lower exposures.

Methods: We replicated the previously applied Cox regression, and examined different time lags, the shape of the concentration–response relationship using penalized splines, and changes in the slope of the relation over time. We then conducted Poisson survival analysis with time-varying effects for smoking, sex, and education.

Results: Since 2001, average PM_2.5 levels, for all six cities, were < 18 µg/m³. Each increase in PM_2.5 (10 µg/m³) was associated with an adjusted increased risk of …