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Amelio began his career with IBM Corporation in 1979 and worked his way up to General Manager Worldwide Operations, Distribution and Reengineering of the Personal Computer Division before leaving for AlliedSignal in 1997.
Between 2000 and 2001, Amelio was Executive President and Chief Operating Officer of NCR Corporation’s Retail Solutions, Financial Solutions, Worldwide Customer Service and Systemedia businesses, responsible for $5 billion in revenue and 27,000 employees worldwide. He arrived at NCR after a stint with Honeywell International Inc. (formerly AlliedSignal). Between 1999 and 2000 he was the company’s President and CEO in charge of Transportation and Power Systems. Amelio, who started with the firm in 1997, was initially responsible for Turbocharging Systems and reestablished AlliedSystems as the industry leader in the technology.
Between 2005 and 2009 he held the chief executive officer position with Chinese technology company Lenovo Group Ltd., manufacturers of personal computers, laptops, servers and other computer hardware. As Lenovo’s president and CEO, he oversaw the integration of the IBM PC Division, which the company purchased in 2005 for $1.75 billion. Lenovo, with 30,000 employees, experienced an annual revenue growth increase from $13 billion to $15 billion by 2008 under his leadership. During that period the company grew its brand internationally and, for seven successive quarters, had sales profits greater than the market. Amelio's three-year contract was not renewed after Lenovo posted a 2008 fourth quarter loss of $97 million.
In August 2010, Amelio became the CEO of CHC Helicopter Service AS. In February 2015, CHC Group Ltd., the parent company of CHC Helicopter, announced that the board of directors had appointed Karl Fessenden as chief executive officer and a member of the board of directors, replacing William Amelio.
Amelio and his wife Jamie, through the Amelio Foundation, founded Caring for Cambodia  in 2003, a non-profit organization which educates Cambodia children by building schools, training teachers and providing for basic needs. Milestones achieved by 2011 included supporting 5,300 students, training 100 teachers, managing and supporting six schools and stocking four libraries with books and resources. He also adopted two children from Cambodia.
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