BACKGROUND AND OBJECTIVE Maternal smoking increases the risk for preterm birth, low birth weight, and sudden infant death syndrome, which are all causes of infant mortality. Our objective was to evaluate if changes in cigarette taxes and prices over time in the United States were associated with a decrease in infant mortality. METHODS We compiled data for all states from 1999 to 2010. Time-series models were constructed by infant race for cigarette tax and price with infant mortality as the outcome, controlling for state per-capita income, educational attainment, time trend, and state random effects. RESULTS From 1999 through 2010, the mean overall state infant mortality rate in the United States decreased from 7.3 to 6.2 per 1000 live births, with decreases of 6.0 to 5.3 for non-Hispanic white and 14.3 to 11.3 for non-Hispanic African American infants (P < .001). Mean inflation-adjusted state and federal cigarette taxes increased from $0.84 to $2.37 per pack (P < .001). In multivariable regression models, we found that every $1 increase per pack in cigarette tax was associated with a change in infant deaths of -0.19 (95% confidence interval -0.33 to -0.05) per 1000 live births overall, including changes of -0.21 (-0.33 to -0.08) for non-Hispanic white infants and -0.46 (-0.90 to -0.01) for non-Hispanic African American infants. Models for cigarette price yielded similar findings. CONCLUSIONS Increases in cigarette taxes and prices are associated with decreases in infant mortality rates, with stronger impact for African American infants. Federal and state policymakers may consider increases in cigarette taxes as a primary prevention strategy for infant mortality.