Medvedev was on top form in a high-quality encounter, winning 5-7, 6-4, 6-1 to secure his first trophy of the season and the eighth of his career.
Nadal, who claimed his 1,000th career victory by beating Feliciano Lopez on Wednesday, is bidding for a first Paris indoors triumph which would draw him level with Novak Djokovic on a record 36 Masters titles.
ATP Finals 2019: Novak Djokovic gunning for sixth year-end title, wresting control of World No 1 ranking from Rafael Nadal
Djokovic is bidding to equal Pete Sampras' record of finishing six years as the world's best player, while Nadal is looking to achieve the feat for the fifth time
Paris Masters 2019: Novak Djokovic claims record-extending fifth title with dominant 6-3, 6-4 victory over Denis Shapovalov
Top seed Djokovic claimed a dominant 6-3, 6-4 victory over his 20-year-old opponent, who looked nervous after being the beneficiary of Rafael Nadal's withdrawal before their scheduled semi-final
Paris Masters 2019: Rafael Nadal eases past Stan Wawrinka; Novak Djokovic sets up quarter-final clash with Stefanos Tsitsipas
Rafael Nadal and Novak Djokovic continued their battle for the year-end world number one ranking on Thursday as both players reached the Paris Masters quarter-finals with wins over Stan Wawrinka and Kyle Edmund respectively
US Open 2019: Roger Federer left disappointed after shock five-set loss to Grigor Dimitrov in quarter-final
Roger Federer struggled to hide his disappointment after his bid for a first US Open title since 2008 ended abruptly with a five-set loss to Grigor Dimitrov in the quarter-finals.
Australian Open 2019: Smashing racket to pieces 'made me feel better,' says eliminated fourth-seed Alexander Zverev
Zverev was tipped as a future Grand Slam champion after a breakthrough 2018 that saw him win the ATP Tour Finals, beating Novak Djokovic and Roger Federer in the process.
Australian Open 2019: Ice-cool Milos Raonic sails into the quarter-finals as Alexander Zverev implodes under pressure
Milos Raonic kept his cool to reach the quarter-finals on Monday as young Alexander Zverev went into meltdown and crashed out of the Australian Open
Monte Carlo Masters: Rafael Nadal sets up quarter-final clash with Dominic Thiem; Novak Djokovic bows out
Nadal has lost twice to Thiem on clay, but produced a dominant display in the French Open semi-finals last year en route to his 10th Roland Garros title.
Australian Open 2018: Novak Djokovic compares tennis to an industry, expresses concern for players' welfare
Djokovic said there should be rational conversations about rules that are imposed and that concern players' well-being.
Australian Open 2018: For wonderkid Alexander Zverev, everything at home is same despite rapid ascent
Zverev announced himself with a third-round appearance at the tournament in 2017, giving Spanish great Nadal a huge five-set scare before bowing out with general acclaim.
ATP Finals: Roger Federer dismisses Rafael Nadal's demands for clay, says indoor hard-court fair for all
Asked about Nadal's desire for a clay finale to the season, Federer insisted the current surface was a good choice given the preponderance of other events on clay.
Paris Masters: Filip Krajinovic rallies past John Isner to reach final, ends American's ATP World Tour Finals bid
Krajinovic was 3-0 down in the deciding-set tiebreak but he kept his composure to prevail on the first match point.
Rohan Bopanna & Jeevan Nedunchezhiyan, along with Purav Raja and Divij Sharan, created history by setting up the first all-Indian doubles final on ATP tour.
Andy Murray and Novak Djokovic will slug it out for the world number one ranking in a high-stakes final at the ATP Tour Finals after completing their contrasting paths to the dramatic showdown.
Novak Djokovic crushed David Goffin 6-1, 6-2 at the ATP Tour Finals on Thursday as the world number two kept his foot on the gas in the race to finish the year atop the world rankings.
Stan Wawrinka admits Andy Murray and Novak Djokovic have set such high standards that he doesn't even think about moving above them in the world rankings.
Andy Murray and Novak Djokovic will stage a dramatic battle to finish 2016 on top of the world as the two old rivals aim for the title at the ATP Finals.
Novak Djokovic has set his sights on regaining the world number one ranking and silencing the doubters by winning the ATP Tour Finals for a record-equalling sixth time.
Rafael Nadal said he may call an early halt to his season and hit the practice courts instead as he bids to be well prepared for next season.