Dr. Scott Gottlieb became commissioner of the Food and Drug Administration in 2017 with an ambitious plan to reduce cigarette smoking, a habit that kills nearly half a million Americans each year, by shifting smokers to less harmful alternatives like e-cigarettes.

But he was quickly embroiled in an unexpected crisis: the explosion of vaping among millions of middle and high school students, many of whom were getting addicted to nicotine.

Dr. Gottlieb will depart at the end of this month, following his sudden announcement last week that he would resign, with his plans to toughen regulation of both vaping and smoking unfinished and powerful lobbying forces quietly celebrating the exit of a politically canny administrator who aggressively wielded his regulatory powers.

Opponents are already swooping in, making their case to Congress and reaching out to the White House. A coalition of conservative organizations that oppose government intervention in the marketplace has harshly criticized Dr. Gottlieb’s crackdown on e-cigarettes. Retailers, including convenience store and gas station owners, are on Capitol Hill lobbying against guidelines Dr. Gottlieb proposed on Wednesday to restrict sales of most flavored e-cigarettes to separate adult-only areas and to require age verification of customers.