Holders Peterborough United were knocked out of the Johnstone's Paint Trophy at the first round stage as Leyton Orient clinched a 3-2 victory in front of just over 3,000 fans at London Road.
Marcus Maddison, on his home debut, sent a shot wide of the target on three minutes as Darren Ferguson's men made a confident start.
However, it was the visitors who opened the scoring, a free-kick was met powerfully by Chris DAGNALL who's header flashed past goalkeeper Alnwick.
A neat interchange between Conor Washington and Michael Smith created a shooting opportunity for the latter, but the left-back dragged his shot inches wide of the near post.
David Mooney's looping header clipped the outside of the post on 10 minutes as Posh were at sixes and sevens with their defensive line following a clipped ball to the back post.
In a lively opening, Kyle Vassell was superbly denied by goalkeeper Woods with the shot-stopper tipping the striker's left-footed effort away from danger.
On the quarter hour mark, Posh drew themselves level and it was a stunning strike on his home debut for Marcus MADDISON who rifled home from 25-yards into the bottom corner of the net.
A speculative effort from Payne was fumbled around the post by Woods while at the other end, Brisley produced a superb block to deny Pritchard.
James was booked for a high challenge on Posh skipper Jack Payne on the half hour mark. Maddison fired wide with a left-footed free-kick two minutes before the break as the Vanishing Spray made it's debut at London Road.
The O's didn't take long to re-take the lead, two minutes after the re-start, Chris DAGNALL got wrong side of Burgess and fired an unstoppable half volley past goalkeeper Alnwick.
Alnwick pushed a deflected Dagnall shot around the post moments later as the O's continued to dominate in the early exchanges of the second period.
Matty James fired over with a free-kick after Brisley was booked for a tug back on Pritchard. Posh introduced Luke James on the hour mark with Kyle Vassell the man to make way.
The O's extended their lead moments later as a low cross was flicked home at the near post by Bradley PRITCHARD.
Maddison fired over with a free-kick on 67 minutes as Grant McCann replaced Payne in midfield. Alnwick produced a fine save to deny Pritchard on the break and moments later, the visitors were reduced to 10-men as Vincelot was quite rightly shown a second yellow card for hacking down Maddison.
Anderson fired wide with his left-foot after cutting inside from the right as Posh tried to reduce the arrears. James was superbly denied by Woods as his glancing header appeared to be heading for the corner.
Sponsors Man of the Match Maddison whistled a shot inches past the post just before the end as Posh tried to grab a consolation. Deep into stoppage time, Posh did grab a goal back as Barnett's header was pushed out and debutant Luke JAMES stabbed the ball over the line.
Final Score: Posh 2-3 Leyton Orient
Posh: Alnwick, Smith, Brisley, Payne (sub McCann 67min), Vassell (sub James 60min), Washington, Anderson, Newell, Ferdinand (sub Barnett 79min), Burgess, Maddison. Unused subs: Walker, Santos.
Leyton Orient: Woods, Vincelot, Cuthbert, Baudry, James (sub McAnuff 60min), Mooney, Lowry, Clarke, Pritchard, Bartley, Dagnall (sub Lee 87min). Unused subs: Legzdins, Henderson, Ling.
Attendance: 3,149 (166 Orient fans)