Injury-plagued Argentinean Juan Martin del Potro's comeback was spoiled by Vasek Pospisil, who advanced to the Miami Open second round via a 6-4 7-6 (9-7) win on Thursday.
Del Potro was set to receive a wildcard into the BNP Paribas Open in Indian Wells last week before withdrawing at the 11th hour due to ongoing wrist issues.
However, Del Potro - ranked 616th in the world - returned to the court for the first time since playing at the Apia International in Sydney in January, albeit unsuccessfully.
Del Potro came unstuck serving for the second set at 5-4 as Pospisil broke before the Canadian saved two set points to claim his first win at the ATP 1000 tournament in Miami.
"I have to take the positive things in my comeback," Del Potro said afterwards.
"I just played another official match after one year, and it's a good signal for the future...I don't have any physical problems after the match, and I will be recovering soon for the future."
Next up for Pospisil is ninth seed Grigor Dimitrov.
Alexandr Dolgopolov, Martin Klizan, Jerzy Janowicz and Borna Coric were among the first-round winners on Thursday.
Dolgopolov required a little over an hour to dispose of Ricardas Berankis 6-4 6-1, earning a showdown with 16th seed Tommy Robredo in the second round.
Klizan faces a daunting clash with world number one Novak Djokovic after seeing off Paolo Lorenzi 6-3 6-4, having capitalised on four of seven break-point opportunities.
Janowicz accounted for Edouard Roger-Vasselin 6-4 6-2, with 13th seed Roberto Bautista Agut his opponent in the next round.
Young gun Coric outlasted Andreas Haider-Maurer 1-6 6-3 7-6 (7-3) to secure a second-round encounter against 18th seed David Goffin.
Elsewhere, Teymuraz Gabashvili overcame a slow start to beat Pablo Andujar 0-6 7-6 (7-4) 6-3.
Veteran Mikhail Youzhny will play fourth seed Kei Nishikori following his 4-6 6-2 6-3 comeback win over Andrey Golubev.
Simone Bolelli dispatched Marcos Baghdatis 6-2 6-2, Mikhail Kukushkin prevailed 6-4 3-6 6-2 against Steve Johnson and Federico Delbonis edged Jiri Vesely 7-6 (7-4) 3-6 7-5.
Alexander Zverev registered 22 aces and saved six break points as he downed Sam Groth 7-5 6-7 (5-7) 6-4, Andrey Rublev stunned Pablo Carreno Busta 1-6 6-1 6-4 and Malek Jaziri lost 2-6 7-5 7-5 to Steve Darcis.
Alejandro Falla trumped Michael Berrer 6-7 (5-7) 6-4 6-4, Jurgen Melzer defeated Ryan Harrison 7-6 (7-3) 6-3 and Thomaz Bellucci survived to eliminate Lleyton Hewitt 7-5 6-7 (2-7) 6-4.