Zein Abdalla, named president of the company just over two years ago, will retire this year.
The departure of Abdalla, 56, follows that of Brian Cornell, who oversaw PepsiCo's global foods business and took the top job at Target Corp this summer.
There has been no hint that PepsiCo Chairman and CEO Indra Nooyi, 59, is stepping down and the company is on solid footing.
Pepsico Inc, based in Purchase, New York, recently raised its profit outlook for the second time and company shares hit another all-time high Wednesday.
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Debra Crew, head of Pepsi's North America nutrition division, departed in September for RJ Reynolds.
Abdalla joined the company in 1995, working mostly overseas. He was the head of Pepsi's European division when he was named president in 2012.
PepsiCo said in a regulatory filing after the markets closed Thursday that Abdalla had notified the company of his decision to retire, effective December 31.