INTRODUCTION: Flow restrictors are child-resistant packaging innovations designed to limit the amount of liquid dispensed from a medication bottle. In 2011, flow restrictors were added to pediatric liquid single-ingredient acetaminophen formulations. The hypothesis of this study is that implementation would be associated with reduced volume and severity of pediatric acetaminophen exposures reported to the U.S. National Poison Data System. METHODS: This study describes accidental unsupervised ingestions of acetaminophen in children aged <6 years. Exposures were grouped into pre-implementation (pre-period; January 4, 2010-July 17, 2011); transition (July 18, 2011-July 15, 2012); and post-implementation (post-period; July 16, 2012-December 25, 2016) periods. Cumulative and annual rates of change per million units (i.e., bottles) sold were calculated for the pre- and post-periods for acetaminophen and pediatric liquid ibuprofen (comparator without flow restrictors). Pre- to post-period rate ratios were used to compare products and to estimate the potential effect on other over-the-counter medications. Analysis was conducted in 2017 and 2018. RESULTS: The pre- and post-period cumulative acetaminophen exposure rate was 507.2 (95% CI=481.1, 534.6) and 325.6 (95% CI=305.8, 346.7) per 1 million units sold, respectively. Declines in the pre- versus post-period rate ratios were seen for exposures with any effect (0.642, 95% CI=0.591, 0.696) and with clinically significant outcomes (0.728, 95% CI=0.581, 0.913). In the post-period, acetaminophen exposures decreased faster than ibuprofen with a rate of change ratio of 0.936 (95% CI=0.912, 0.960) for all exposures and 0.939 (95% CI=0.909, 0.970) for exposures with any effect. CONCLUSIONS: The addition of flow restrictors to pediatric liquid acetaminophen was associated with a reduction in the number and severity of exposures. Application of flow restrictors to other liquid medications should be considered.