Kerry Kittles couldn't keep up with DeJuan Wheat, and Villanova's season ended in disappointment for the second consecutive year.
Wheat, held without a field goal in the first half, scored 17 of his 19 points after halftime and helped slow Kittles, Villanova's All-American, as Louisville stunned the Wildcats, 68-64, at the Midwest Regional on Sunday.
The Wildcats, first-round losers to Old Dominion last year when they were also seeded third, again failed to reach the Sweet 16 despite facing a tired sixth-seeded Louisville team that needed overtime to beat Tulsa in the first round.
"Of course I'm disappointed. It was my last game," said Kittles, a likely NBA lottery pick. "I expected to get back into the tournament and make things happen. I'm just disappointed, that's all."
With Louisville (22-11) clinging to a 61-59 lead, Tick Rogers made a turnaround jumper from the right baseline with 2:04 left and the Wildcats never got any closer.
Wheat's fadeaway 18-footer over Kittles with 26 seconds left put the Cardinals ahead, 65-60, and his two free throws with 15 seconds remaining made the score 67-62.
Villanova center Jason Lawson, who tied his season high with 23 points, made two free throws with 5.9 seconds left to make the score 67-64, then fouled out on the inbounds to Rogers.
Rogers missed his first free throw, but made the second to send Coach Denny Crum and the Cardinals to their third Sweet 16 appearance in the last four years.
Kittles finished with 20 points, seven in the second half, and the Wildcats (26-7) finished their second consecutive season in frustration.
Alvin Sims scored 14 and Rogers added 13 for Louisville, which led, 32-28, at halftime and never trailed again despite nearly blowing a 13-point lead in the second half.
Wheat had said the whole Louisville team was tired during Saturday's shootaround, while the Wildcats were rested from their first-round blowout of Portland.
But the Cardinals, overachievers all season, got a second wind after a slow start.
Louisville, which overcame a 12-point deficit in the final 3:18 of regulation to beat Tulsa, made only four of its first 15 shots and fell behind, 19-12.
Sims helped bring the Cardinals back, scoring seven points after a timeout to spark a 20-9 run to close the first half.
Louisville stretched its advantage to 49-36 with 13 minutes left on consecutive three-point baskets by Rogers and Wheat.
Wheat, who scored 33 points in 41 minutes against Tulsa, teamed with Sims, Rogers, B.J. Flynn and even center Samaki Walker in holding Kittles scoreless for the first 13:53 of the second half.