Key PointsQuestionDid adults’ use of electronic nicotine delivery systems (ENDS) and cigarette smoking behaviors change after the Center for Tobacco Products (CTP) of the US Food and Drug Administration prioritized enforcement efforts against fruit-flavored cartridge ENDS in February 2020?FindingsThis nationally representative US cohort study found a significant decrease in fruit-flavored cartridge ENDS use among adults in 2020; no differences were found in cigarette cessation or relapse rates between those who used ENDS that were vs were not targeted by the CTP.MeaningFindings provide no indication that the CTP’s 2020 targeted ENDS enforcement priority was associated with reduced smoking cessation or increased smoking relapse among adults who used ENDS.