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The hosts set the tone from the very first whistle and had the lead inside four minutes as quick hands from James Hook made space for Tommy Bowe to score in the corner.
Dan Biggar’s conversion went wide but that miss proved to be his only kicking indiscretion of the half as he added a further 12 points from the kicking tee before the break.
Toby Booth’s side recovered well from their early setback and with the ball in their possession they were able to exert some pressure of their own.
They asked questions of their hosts on both flanks with Sailosi Tagicakibau and Jonathan Joseph announcing themselves to the match with probing runs.
That pressure was soon turned into points just before the 10 minute mark as Ryan Lamb knocked over his first penalty of the evening after Ospreys had infringed at the breakdown.
More Welsh indiscipline four minutes later gave Lamb another platform for points and his accurate kick gave Irish a 6-5 lead.
A penalty from inside his own half from Biggar restored the lead, but the match remained finely in the balance.
Shane Williams nearly brought that equilibrium to an end with a superlative break through the Exiles midfield, only to be stopped just five metres out by the body of Topsy Ojo after he had attempted to hurdle the tackle of the England international.
The Welsh winger’s individual piece of skill roused his team and they duly upped their game and began to play the excellent rugby that earned them the Magners League title last season.
But as has been the habit this season the Exiles’ defence were more than a match for a skillful attack and the Ospreys had to rely on Biggar’s boot and the young fly half didn’t disappoint with four penalties out of four as the hosts took an ominous 17-6 lead into half-time.
Heineken Cup rules permit just 10 minutes for the interval but Booth and his coaching team seemed to have used every second wisely as Exiles were soon back in the match less than two minutes after the restart.
The hero of the piece was Tagicakibau who snatched the ball from an Ospreys attack deep inside his own half and charged down the touchline to score despite the best efforts of James Hook who could only cling to the giant Samoan's shirt as he was dragged 10 metres to the line.
Lamb then did his bit with an excellent kick and that ominous lead was suddenly reduced to just four points.
Ospreys suffered another blow in the build up to the try as the inform Biggar was forced off with injury and with the wind taken out of their sails, a few mistakes began to creep into their game.
But just when they looked in danger of relinquishing their lead, Williams again lit up the match as he scored one of the great Heineken Cup tries.
Spotting space behind the Irish line, he executed a deft chip into it, collected the ball and then sped past three tacklers for a sensational score.
Hook added the extras and then extended his side's lead four minutes later with a well taken penalty to give the hosts a 27-13 lead.
But there was more drama to come as first Lamb reduced the deficit back to 11 points with another penalty and then with eight minutes to play, Jerry Collins was sent to the sin bin leaving his side to play the closing stages a man down.
Despite their best efforts, the Exiles could break down their hosts in the dying minutes as Ospreys held on for a deserved first European win of the season.
Tries: Bowe (3), Williams (53)
Penalty goals: Biggar (15, 32, 35, 40), Hook (57)
Conversions: Hook (53)
Tries: Tagicakibau (41)
Conversions: Lamb (42)
Penalties: Lamb (8, 13, 60);
Scoring sequence (LI first): 0-5, 3-5, 6-5, 6-8, 6-11, 6-14, 6-17 . HT. 13-17, 13-24, 13-27, 16-27.
Ospreys: 15. Lee Byrne; 14. Tommy Bowe; 13. Andrew Bishop; 12. James Hook; 11.Shane Williams; 10. Dan Biggar (Walker, 42); 9. Mike Phillips; 1. Paul James (Bevington, 66); 2. Richard Hibbard (Bennett, 58); 3. Adam Jones; 4. Ryan Jones (Gough, 76); 5. Alun Wyn Jones (captain); 6. Jerry Collins; 7. Marty Holah (Tipuric, 58); 8. Jonathan Thomas.
Replacement not used: Nutbrown, Owen, Walker.
London Irish: 15. Topsy Ojo; 14. Jonathan Joseph (Seveali’i, 70); 13. Seilala Mapusua; 12. Dan Bowden; 11.Sailosi Tagicakibau; 10. Ryan Lamb (Malone, 68); 9. Paul Hodgson ; (Allinson, 76); 1. Clarke Dermody (captain); 2. James Buckland (Paice, 60); 3. Faan Rautenbach (Corbisiero, 51); 4. Nick Kennedy; 5. Bob Casey (Garvey, 60); 6. Kieran Roche; 7. Chris Hala’ufia (Johnson, 68); 8. George Stowers.
Replacement not used: Murphy.