But two Cipriani penalties, the second after Munster prop Marcus Horan was sin-binned for coming in the side of a ruck, brought Wasps to within four points.
Edinburgh stepped up the tempo as half-time approached and they delivered a further dent to the Ospreys when prop Cross claimed the second try from yards out, which was converted by Paterson.
James did well to scoop up the ball as the pass fell just short and the prop earned his reward with a second try, although this one went unconverted.
They were first being denied by the television referee, but prop Rhys Thomas made no mistake at the second attempt.
O'Driscoll will become the second Irish player to win 100 caps, following prop John Hayes who reached the milestone two weeks ago against England.
Nathan Hines moves to the second row and loose-head prop Allan Jacobsen has been declared fit to win his 50th cap.
The turning point, with the game locked at 13-13 midway in the second period, came when Bristol prop Darren Crompton was sin-binned for a high tackle.
The Blues' inspirational skipper and prop Gethin Jenkins failed to re-emerge for the second half, replaced by John Yapp with Martyn Williams taking over as captain.
Matthew Jarvis landed three penalties and prop Geoff Cross claimed the second try of the evening before half-time.
Burger will face a disciplinary hearing on Sunday along with lock Bakkies Botha, who was reported for a dangerous charge on Lions prop Adam Jones early in the second half.
There was more good news for the Cherry and Whites as New Zealand prop Greg Somerville came off the bench to make his debut in the second half.
Alun-Wyn Jones won the race to start alongside captain Paul O'Connell in the second row with Phil Vickery and Gethin Jenkins to prop alongside England hooker Lee Mears.
Leicester pulled away in the second half but only secured their bonus point when replacement prop Rob O'Donnell was sin-binned in the last minute and Crane powered over.
Just two minutes later the Welsh were in for a second, this time through prop Thomas, after Morgan's cross-field kick found Luke Charteris in space and his basketball pass set the front-row on his way.
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Referee Nigel Owens lost patience and sin-binned prop Salesi Ma'afu and the Wallabies duly conceded a second penalty try after their pack had again been taken apart at a five-metre scrum.
After Eastmond's try, England prop James Graham crashed over for his second try of the match and winger Francis Meli added a late score to give Saints a flattering margin of victory.
The prop is out of action until December with a shoulder injury suffered in the second Lions Test against South Africa.
Any hope of an unlikely Blues comeback was soon shattered when De Luca intercepted prop Rhys Gill's lazy pass to score a second try under the posts.
But Scarlets exploited the numbers when visiting prop Ronan Loughney was sin-binned, Jonathan Davies crossing for his second try before Lamont struck.
But, five minutes later, on-loan Salford prop Parker ploughed over for his first try for the club, Arundel got his second on 54 minutes.
However, the home fans were celebrating their second try a minute later when subtle offloads from lock Justin Harrison and prop Duncan Bell set up fellow forward Short, with Davis once again adding the extras.
Loffreda was boosted by the return of England backs Dan Hipkiss and Varndell, along with second row Marco Wentzel and tight-head prop Martin Castrogiovanni.
Howarth missed the conversion but scored Glasgow's second try six minutes later, finding Phil Booth in front of him and easily dancing around the Warriors prop to score.
Young Gloucester prop Wood is rewarded for a fine season while fellow prop Crompton, back rower Buxton and second rows Winters and Schofield are all grizzled veterans on the club scene.
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Dylan Hartley was held just short of the line on 19 minutes but when Bath prop David Flatman was penalised at the resulting scrum, Myler made it 10-6 with his second penalty, only for James to extend his side's lead after the visitors were offside at a ruck.
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