The Croatian had a nine-month ban handed down by the International Tennis Federation's Anti-Doping Tribunal in September reduced to four months by the Court of Arbitration for Sport, meaning he was eligible to return to the ATP Tour in Paris this week.
Cilic had to come back from a set down against qualifier Sijsling before eventually edging out the Dutchman 5-7 6-1 6-4.
The 25-year-old, who received his suspension after testing positive for a banned stimulant at the BMW Open in Munich in May, was particularly impressive on serve as he fired down 21 aces, despite his first-serve percentage at only 48 per cent.
Next up for Cilic is world number five Juan Martin del Potro, who will be looking to carry on the momentum from his Swiss Indoors win in Basle last week with the ATP World Tour Finals just around the corner.
Feliciano Lopez came through a two-hour 23-minute epic against Australian qualifier Bernard Tomic.
The Spaniard was a 6-4 6-7 (4/7) 7-6 (7/1) winner to set up a second-round clash against Stanislas Wawrinka, who will be hoping to book his place in the Tour Finals this week.
Lopez's compatriot Fernando Verdasco squeaked past Latvian Ernests Gulbis 7-6 (7/3) 7-6 (7/5) and will next face Richard Gasquet, another contender for the end-of-year tournament in London.
Japan's Kei Nishikori was impressive in seeing off home hope Julien Benneteau 6-4 6-2, while Benoit Paire was dismissed 6-2 6-2 by Pierre-Hugues Herbert in an all-French match-up.
Lukas Rosol sealed a straightforward 6-3 6-4 win over Jeremy Chardy, Robin Haase dispatched Denis Istomin 7-6 (10/8) 6-3, Santiago Giraldo upset the higher-ranked Adrian Mannarino 6-3 2-6 6-4, while Philipp Kohlschreiber overcame Andreas Seppi 6-3 3-6 6-4.