The left-hander who missed the entire major league season last year after shoulder surgery pitched 2 2/3 innings without allowing an unearned run on Sunday in the Mets' rain-shortened 4-2 loss to the Miami Marlins.
The game was called after the fifth inning. Miami shortstop Jose Reyes, who left the Mets to sign with the Marlins in the offseason, did not make the trip.
"We're still building up pitches," Santana said. "I think once we get 80 to 90 pitches and do it every five days, that's when we'll say we're good."
The start was the second in exhibition play this spring for Santana. The two-time Cy Young winner had surgery in September 2010 and briefly pitched in the minors last year.
Santana gave up two hits and an unearned run in his 42-pitch outing, walking two and striking out one. The run against him came in the third after an error by third baseman Ronny Cedeno.
"I truly believe we're going to do this right and that Johan Santana will be on this team opening day," Mets manager Terry Collins said.
"He'll add 15 (pitches) to his next start, so he'll be at 60, 65. Next time out it'll be 80," he said. "What I'm seeing right now is a guy who's starting to get comfortable on the mound. He was just missing today, just off the plate."
"All is good, Ready to go!" Stanton tweeted. "No worries my people."
Miami starter Mark Buehrle made his first spring outing against major league hitters. He gave up two runs and five hits in four innings. Buehrle faced the University of Miami at Marlins Park on March 6.
"They were hitting the ball hard. I like to get softer outs," Buehrle said.
"I fell behind in the count a few times, and my changeup wasn't the greatest, but overall I felt good and got my pitches in," he said.
Buehrle gave up two runs and five hits.
"I made it through four innings. That was the main goal," he said.
The free-spending Marlins signed Buehrle as a free agent in December. The 32-year-old Buehrle pitched all 12 of his previous seasons with the Chicago White Sox.