Vaughan - who won the toss on his Yorkshire home ground - put on 53 for the second wicket with Alastair Cook following the early loss of Andrew Strauss.
But left-hander Cook - one of four England centurions in the first innings of the drawn first Test at Lord's - was out for 42 to the last ball before lunch, lbw to off-spinner Chris Gayle.
Vaughan, who had not played a Test for 18 months, had faced 62 balls with four fours.
England saw Strauss drop the first ball of the morning from Daren Powell just in front of Daren Ganga at short leg. But the left-hander was more assured when, given width, he twice square cut Powell for four.
However, attempting another cut off Powell, he got an edge and was caught behind by wicket-keeper Denesh Ramdin for 15 to leave England 38 for one in the ninth over.
Strauss's exit brought in Vaughan for his first Test since playing against Pakistan at Lahore in December 2005 after being ruled out with knee and hamstring problems.
A broken finger, sustained while batting for Yorkshire against Hampshire three weeks ago, kept him out of the drawn opener of a four-match series at Lord's.
Vaughan, 32, got off the mark when he turned Powell through square leg. Powell, after an opening spell of one wicket for 24 runs in six overs, was replaced by Jerome Taylor.
At the other end, Corey Collymore bowled tightly with his first seven overs costing 21 runs. Vaughan, becalmed on three for 27 balls, moved to seven with a trademark pull in front off square off Powell, in his second spell.
He played the shot of the morning when he off-drove Taylor for four before turning him off his legs for another boundary.
England's other change from Lord's saw Ryan Sidebottom, six years after playing his one and only previous Test, recalled in place of injured quick Matthew Hoggard.
West Indies suffered a blow here Friday when Shivnarine Chanderpaul, their senior batsman who top scored with 74 in the tourists' first innings at Lord's, was ruled out with tendonitis in his right knee.