Objective To examine the associations of partial and comprehensive smoke-free legislation with neonatal and infant mortality in Brazil using a quasi-experimental study design.

Design Monthly longitudinal (panel) ecological study from January 2000 to December 2016.

Setting All Brazilian municipalities (n=5565).

Participants Infant populations.

Intervention Smoke-free legislation in effect in each municipality and month. Legislation was encoded as basic (allowing smoking areas), partial (segregated smoking rooms) or comprehensive (no smoking in public buildings). Associations were quantified by immediate step and longer term slope/trend changes in outcomes.

Statistical analyses Municipal-level linear fixed-effects regression models.

Main outcomes measures Infant and neonatal mortality.

Results Implementation of partial smoke-free legislation was associated with a −3.3 % (95% CI −6.2% to −0.4%) step reduction in the municipal infant mortality rate, but no step change in neonatal mortality. Comprehensive smoke-free legislation implementation was associated with −5.2 % (95% CI −8.3% to −2.1%) and −3.4 % (95% CI −6.7% to −0.1%) step reductions in infant and neonatal mortality, respectively, and a −0.36 (95% CI −0.66 to−0.06) annual decline in the infant mortality rate. We estimated that had all smoke-free legislation introduced since 2004 been comprehensive, an additional 10 091 infant deaths (95% CI 1196 to 21 761) could have been averted.

Conclusions Strengthening smoke-free legislation in Brazil is associated with improvements in infant health outcomes—particularly under comprehensive legislation. Governments should accelerate implementation of comprehensive smoke-free legislation to protect infant health and achieve the United Nation’s Sustainable Development Goal three.