Nishikori secured a 6-4, 6-4 win in one hour and 34 minutes but he did not have it all his own way against the world No 66.
The pair exchanged early breaks in the opening set before Nishikori struck to break again in the tenth game and snatch the advantage in the match.
Andujar responded by breaking Nishikori immediately at the start of the second, but Nishikori fought back to break and level the set at 4-4.
His second break of the set sealed victory for the world No 5 and made him the seventh player to retain the Barcelona title in the Open era.
“I didn’t look to defend my title, just to play my best,” Nishikori said. “I knew that this was a tough tournament with all the Spanish players. I just tried to play my best and now I am really happy.”
Nishikori hit 23 winners to 19 for Andujar. “I knew that he had a great backhand down the line too, so I had to move the ball around, and in the last two games I played really well,” Nishikori added.
“On match point I just closed my eyes and hit it.”
Despite losing in two sets, Andujar gave Nishikori his toughest test of the tournament a day after upsetting third-seeded David Ferrer.
“I think the difference was that I didn’t take advantage of the chances I had in the second set,” said the Spaniard, who had won his only previous meeting with Nishikori on clay.
In Bucharest, meanwhile, Spaniard Guillermo Garcia-Lopez claimed the fifth ATP Tour title of his career with victory in the BRD Nastase Tiriac Trophy.
The fifth seed was pushed hard by Czech youngster Jiri Vesely who fought back from 3-0 down to serve for the first set.
But 31-year-old Garcia-Lopez kept his nerve to fight back and take the opener before prevailing in an even tighter second set for a 7-6 (5), 7-6 (11) win.
“It was complicated for me to close the match,” said Garcia-Lopez. “I was feeling nervous, a lot of things crossing my mind, but in the end I was happy to win. It is the first time in my career that I’ve won two titles in a year.”
On the women’s circuit, German left-hander Angelique Kerber kept her nerve in a thrilling final set to edge past Caroline Wozniacki and win the Porsche Tennis Grand Prix in Stuttgart.
Kerber, a second-round conqueror of top seed Maria Sharapova, twice found herself a break down in the decider before rallying to triumph 3-6, 6-1, 7-5.
Danish fourth-seed Wozniacki had moved in front by taking the first set in 32 minutes but Kerber responded in style to level up. Wozniacki led 3-1 in the third set and then 5-3 as she moved within two points of victory, before Kerber hit back to take the title in a match lasting just under three hours.
“In the end I needed all my reserves. I’m really, really proud to have managed it in front of my home crowd,” said Kerber after claiming her first WTA title at home and her fifth overall.
Wozniacki, who lost the 2011 final to another German, Julia Goerges, but had been hitting form after claiming her 23rd title in Kuala Lumpur last month, said: “It was small things today that made the difference. I had 5-3 in the third set and 30-all, and it could have gone both ways, but she took her chances and it went her way.”