"Having done everything to ensure stability and make a smooth transition of power possible, I decided to step down from the post of prime minister of Ukraine," the 41-year-old pro-Western cabinet chief said in a video address.
The tough-talking prime minister's decision comes barely two months after he survived a no-confidence vote in his government.
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He said President Petro Poroshenko's party had already nominated parliament speaker Volodymyr Groysman to his post and that he would not stand in the way.
"From today onwards, I see my goals in a broader light than just heading the government," said Yatsenyuk.
He vowed to push through "new election legislation, consitutional reform, legal reforms, a coalitions controlling the future government's course, international support for Ukraine, and its membership in the European Union and NATO".
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But he failed to mention what possible future role he saw for himself in Ukrainian politics.
His condemnation of Russia's alleged backing of the two-year pro-Moscow uprising in eastern Ukraine and ability to clinch a crucial IMF rescue package in early 2015 helped Yatsenyuk's party become parliament's second largest in October 2015 polls.
He formed a parliamentary coalition with the president's bloc and several junior partners that was able to push through some tough and very unpopular belt-tightening measures prescribed by the International Monetary Fund.
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But his party's approval rating has slumped to a mere two percent both because of the painful economic reforms and his perceived inability to tackle state graft.
Yatsenyuk's decision means that Ukraine will in the coming days be headed by a brand-new government that has also vowed to persue the former Soviet nation's current pro-Western course.
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