The Seoul High Court upheld the lower court's ruling dismissing all the charges from a case involving a 2015 merger that prosecutors said was designed to cement his control of the tech giant.
The legal battles have been a distraction for Lee, who faced growing questions about his ability to lead Samsung Electronics - the world's top memory chip and smartphone maker - as it grapples with growing competition and lacklustre stock prices.
"It took a long time. We hope with the latest ruling, the defendants would be able to focus on their work," Lee's lawyer Kim You-jin said after the ruling.
For nearly a decade, Lee has faced legal challenges, including those from the merger that paved the way for his succession after his father, Lee Kun-hee, had a heart attack in 2014.
A lower court last year cleared Lee of all charges related to the 2015 $8 billion merger between two Samsung affiliates, Samsung C&T 028260.KS and Cheil Industries.
Prosecutors later appealed to the Seoul High Court, seeking a five-year jail term, citing a separate ruling in August that said Samsung BioLogics, an affiliate of Cheil Industries, breached accounting standards by overstating its assets to justify the merger.
Lee did not answer questions from reporters when he was leaving court on Monday.
He has denied wrongdoing, saying in court last November, "I never intended to deceive or damage investors for personal gain".
It was not immediately clear whether the prosecution would appeal the decision to the Supreme Court.
Samsung shares were little changed after news of the ruling, trading down 2.7% in afternoon trading.