The London 2012 heptathlon champion, whose last hurdles race was at the Olympic Stadium last summer, clocked 13.08 seconds.
The time was certainly nothing to write home about - it was more than half a second slower than she ran at the Olympics - but most importantly she appeared to come through unscathed.
The 26-year-old finished fourth, with Olympic champion Sally Pearson of Australia winning in 12.65secs.
The Sheffield athlete admitted yesterday how she fared at the Sainsbury's Anniversary Games would be the acid test of her fitness for the World Championships, now just two weeks away, following the Achilles tendon which has played havoc with her season.
Elsewhere, Mo Farah gave the Olympic Stadium crowd another 'Super Saturday' performance as a devastating final lap earned him victory over 3,000 metres at the Sainsbury's Anniversary Games.
The double London 2012 champion hit the front with around 500m to go and from then on there was no stopping him as he came home in seven minutes 36.85 seconds.
David Moorcroft's 31-year-old British record of 7mins 32.79secs was never on the cards, but the bumper crowd which roared Farah on could not have cared less.
American Ryan Hill finished second, more than five seconds behind the Briton.
Ennis only started hurdling again in training last week, so lacked some of usual power, but there was cause for optimism.
Ennis-Hill told the BBC: "This was very nerve-wracking. I've not been able to compete in the hurdles since the Olympics.
"It's great to see the crowd and recover the memories, but I'm disappointed with my time.
"I'm lacking speed work. I've started hurdling this week and it was to be expected.
"I'm going to have a chat with my coach, sit down and see where we are."
Her coach Toni Minichiello was less hard on his charge.
He said: "There's no-one on her left side (she ran from lane eight with lane seven empty), which meant she lost contact with other athletes.
"It's where you'd expect her to start a season, not being an out-and-out hurdler.
"I hope it's ring-rust, but there's a need for another race before (the World Championships in) Moscow.
"You'd want a time of round about 12.8 and that's do-able."
Great Britain's Tiffany Porter was second in the race in 12.76.
Ennis-Hill only made her comeback on Tuesday, with a javelin and long jump competition in Loughborough, and has been pleased with how the injury has reacted.
The heptathlete was back at the stadium a year to the day since the Olympic opening ceremony and looking to help re-create memories of 'Super Saturday', when she, Mo Farah and Greg Rutherford all won gold in the space of 45 minutes.
Ennis-Hill was greeted by a huge roar when she came up on big screen, with the capacity crowd raising the decibel level for her actual introduction.
Farah got a similar reception when he was welcomed before the action got under way.
His entrance was rather less spectacular than Usain Bolt's rocket ride into the stadium last night, but he was still greeted to the sight of 50,000 people performing his signature Mobot pose at the same time.
Farah was due to race over 3,000m later this afternoon, with Dave Moorcroft's British record under threat.
Long jumper Rutherford was absent through injury, though.
Christine Ohuruogu, the Olympic 400m silver medallist, made a winning return with a season's best 50.00, the fastest she has ever run outside a major championships.
The 29-year-old was challenged by American Francena McCorory in the home straight, but was strong enough to hold her off, winning by 0.13.
Ohuruogu has been so keen to keep the Olympic legacy alive at grass-roots level in her home borough of Newham she has set herself a task of visiting every school in the area over the next two years.
Chris Tomlinson failed to boost his chances of long jump selection ahead of Rutherford for the World Championships as he could only manage a best of 7.99m for fifth place.
The long jump selection was delayed and will be announced on Tuesday, with the pick between either Tomlinson or Rutherford since neither have the A qualifying standard.
Four of Tomlinson's six jumps today were fouls. He said: "It would have been nice to jump 8.25m (the A standard) and made my life a little bit easier but unfortunately, although the distances were there, I kept seeing the red flag."
Rhys Williams finished sixth in the 400m hurdles in 48.97, while Anyika Onuora continued an impressive meet for the hosts' women sprinters with a personal best 22.79 for fourth in the 200.
Allyson Felix, the triple London 2012 gold medallist, won in 22.41.
Kenya's Augustine Choge won the Emsley Carr mile in 3:50.01.
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