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Maternal smoking has repeatedly been associated with increased infant mortality rates. No study has investigated whether smoking cessation influences the risk of infant death. This study estimates infant mortality after the second pregnancy in relation to smoking behavior in both the first and the second pregnancy.We used the Swedish Medical Birth Register to identify women who delivered their first and second singleton infants during 1983–2002. Maternal smoking during the 2 pregnancies was categorized into (1) never smoker, (2) quitter, (3) starter, and (4) persistent smoker. In the second pregnancy, 555,046 live births (of at least 22 completed gestational weeks) were followed for infant death within 1 year. Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).Compared with infants born to never smokers, the HR (95% CI) of infant mortality in the second pregnancy was 2.0 (1.7–2.4) among infants born to persistently heavy smokers, whereas among women who stopped smoking in the second pregnancy, the HRs were 1.4 (1.0–2.0) among those who had been heavy smokers in the first pregnancy, and 1.0 (0.8–1.2) among those who had been light smokers. The association of smoking during pregnancy with infant mortality was modified by infant's age, and was strongest at 4–15 weeks after birth. The smoking effect on neonatal mortality, but not postneonatal mortality, was mediated by gestational age.Smoking cessation reduced the risk of infant death. The smoking-related risk of neonatal mortality appears to be mediated by smoking effects on gestational age, a factor that only partly explains the association between smoking and postneonatal mortality.