Many studies have reported associations between daily particles less than 2.5 µm in aerodynamic diameter (PM2.5) and deaths, but they have been associational studies that did not use formal causal modeling approaches. On the basis of a potential outcome approach, we used 2 causal modeling methods with different assumptions and strengths to address whether there was a causal association between daily PM2.5 and deaths in Boston, Massachusetts (2004-2009). We used an instrumental variable approach, including back trajectories as instruments for variations in PM2.5 uncorrelated with other predictors of death. We also used propensity score as an alternative causal modeling analysis. The former protects against confounding by measured and unmeasured confounders and is based on the assumption of a valid instrument. The latter protects against confounding by all measured covariates, provides valid estimates in the case of effect modification, and is based on the assumption of no unmeasured confounders. We found a causal association of PM2.5 with mortality, with a 0.53% (95% confidence interval: 0.09, 0.97) and a 0.50% (95% confidence interval: 0.20, 0.80) increase in daily deaths using the instrumental variable and the propensity score, respectively. We failed to reject the null association with exposure after the deaths (P =0.93). Given these results, prior studies, and extensive toxicological support, the association between PM2.5 and deaths is almost certainly causal.