Medvedev had withdrawn from two recent tournaments due to fatigue and a right foot injury, making this the top-seeded Russian's first on-court appearance since losing to Jannik Sinner in the Australian Open final.
Medvedev advances to face Italian Lorenzo Sonego, who posted a 6-4, 5-7, 6-1 win over Sumit Nagal of India. The latter saved two break points at 5-5 in the second before running out of steam in the third set of the 2-hour, 19-minute match.
Fourth-seeded Karen Khachanov breezed to a 6-2, 6-3 win over Frenchman Luca Van Assche.
France's Ugo Humbert, the fifth seed, posted a 4-6, 6-3, 6-3 win over countryman Gael Monfils and eighth-seeded Alejandro Davidovich Fokina of Spain seized a 6-3, 4-6, 6-1 victory over Fabian Marozsan of Hungary.
Movistar Chile Open
Italy's Luciano Darderi emerged with a dramatic 7-6 (4), 6-7 (6), 7-6 (5) victory over Argentina's Facundo Bagnis in the first round at Santiago, Chile.
In a match that lasted 3 hours, 19 minutes, each player broke serve just once, both in the second set. Darderi failed to take advantage of two match points in the second-set tiebreaker.
In the third-set tiebreaker, Darderi jumped on top 5-2. Bagnis won the next three points to pull level before Darderi won the final two points.
Earlier Tuesday, Argentine qualifier Juan Manuel Cerundolo upset fifth-seeded Yannick Hanfmann of Germany 3-6, 6-3, 7-5. Eighth-seeded Jaume Munar blitzed Spanish countryman Bernabe Zapata Miralles 6-4, 6-1.
In an all-Chilean matchup, Tomas Barrios Vera defeated Cristian Garin 7-6 (3), 7-5. Other first-round winners were Argentina's Thiago Agustin Tirante, Peru's Juan Pablo Varillas, Spain's Albert Ramos-Vinolas and Brazil's Thiago Seyboth Wild.
Abierto Mexicano Telcel
Daniel Altmaier upset top-seeded Alexander Zverev 6-3, 3-6, 6-3 in an all-German first-round match at Acapulco, Mexico.
Altmaier shook off six of the seven break points on his serve in a match that featured just one break per set. The decisive break came in the second game of the third set, and Altmaier held on to eliminate the 2021 Acapulco champion.
In other action, eighth-seeded Frances Tiafoe rallied for a 4-6, 6-3, 6-0 win over Australia's Max Purcell.
Purcell had statistical advantages in winners (29-23), aces (11-4) and fewer unforced errors (11 to Tiafoe's nine), but Tiafoe came through in the key moments, saving seven of the eight break points on his serve.
Second-seeded Holger Rune of Denmark blasted U.S. qualifier Michael Mmoh 6-2, 6-3, and fifth-seeded Stefanos Tsitsipas of Greece blitzed Russia's Roman Safiullin 6-3, 6-4. Sixth-seeded Casper Ruud of Norway edged the United States' Christopher Eubanks 6-4, 6-7 (5), 6-3. Germany's Dominik Koepfer eliminated French qualifier Terence Atmane 6-4, 4-6, 6-0.
U.S. qualifier Aleksandar Kovacevic eliminated Jordan Thompson 6-3, 5-7, 6-4 three days after the Australian won the Mifel Tennis Open in Los Cabos, Mexico. Serbia's Dusan Lajovic cruised past Mexican wild card Rodrigo Pacheco Mendez 6-2, 6-2.
