Cilic, seeded No. 5 this year, defeated Dusan Lajovic 6-4, 7-5 with 12 aces that helped him win 70 percent of the points on serve. Cilic won the event in 2009, '10 and last year.
Cilic lost his serve once Wednesday but had three breaks to head into the quarterfinals where he'll go against either fourth-seeded Ivan Dodig or Ivo Karlovic. Karlovic tied an ATP record with 44 aces Tuesday in his first-round match.
The other matches in Zagreb Wednesday were all first-rounders, including Dudi Sela's 6-3, 7-6 (7-2) upset of sixth-seeded Lukas Rosol.
Eighth-seeded Igor Sijsling had a pair of third-set breaks to get by Blaz Kavcic 6-7 (4-7), 6-3, 6-4.
Qualifier Andrey Kuznetsov beat Sergiy Stakhovsky 6-4, 7-6 (10-8) and Andrey Golubev edged Victory Hanescu 7-6 (8-6), 4-6, 7-6 (7-5).