Spurs handed a debut to January recruit Gilberto at left-back, while Jonathan Woodgate and Ledley King were both passed fit to return at the heart of defence.
The opening minutes of the game saw neither keeper forced into serious action, with PSV content to sit back and try to make sure of a clean sheet.
Fifteen minutes in the first effort on goal arrived as Jan Kromkamp fed Jefferson Farfan and he scuffed a tame effort straight at Paul Robinson.
Farfan threatened again just before the half-hour mark, winning a free-kick against Gilberto and seeing the resultant set-piece deflected behind for a corner.
He made no mistake 11 minutes before the break as Gilberto gave the ball away 30 yards from goal and Farfan advanced to curl a right-foot shot past the despairing dive of Robinson from the edge of the area.
That setback sparked the home side into action, with Steed Malbranque seeing one effort deflected narrowly wide, while another was blocked by PSV keeper Heurelho Gomes.
Malbranque then fired wide after a flowing Spurs move, before Woodgate headed a yard wide of the far post from eight yards from a Jermaine Jenas cross from the left.
The half drew to a close with Robbie Keane doing superbly to get away from two markers, before Gomes denied him with an outstanding one-handed save.
After the restart, Farfan was again the main danger for Spurs, having drifted out to the PSV right to test Jamie O'Hara, who replaced Gilberto at half-time.
On the hour Farfan led a quickfire counter-attack and fed Ibrahim Afellay on the edge of the area, but he sliced his left-foot shot well wide of target when he should have done much better.
Soon after, Jenas had to leave the pitch on a stretcher with a nasty-looking ankle injury.
Farfan continued to impress for the visitors and the Spurs rearguard only got a breather when he was substituted five minutes from time.
Straight away home sub Adel Taarabt lifted a pass to the left, O'Hara met it on the volley and his left-foot effort flashed inches wide of the far post with Gomes beaten.
Dimitar Berbatov and Keane were both denied by Gomes in the dying minutes as PSV held out for a deserved victory, having given a disciplined display against the newly-crowned Carling Cup winners.