But Madonna, 57, put on a slick routine where two dancers pulled off her trailing pink cape with one quick tug and the star stayed on her feet.
Dressed in an array of costumes, she sang new material from her latest album as well as classic hits including Material Girl, before finishing with a rendition of Holiday.
The star was even joined for a lively dance on stage with TV host Graham Norton.
Madonna told the crowd: 'I've been married twice and I suck at marriage so far. But there's always hope. I haven't given up on love. I don't want you to be thinking I'm cynical about love. I haven't given up on love at all. In fact, it's my life's dream to find the perfect love. Until then I am married to all of you.'
Talking about hardship in the world, she said: 'It does make me want to cry sometimes. I know that we, the people, if we're unified and we are together and we have love, we can conquer anything. And I'm not being idealistic. I truly believe that.'
The star got laughs from the crowd when she said she needed a rest more than halfway through her energetic show. 'It's so nice to sit down for a wee moment. You don't mind do you? Oh my goodness. Even I have to admit that I outdo myself,' she joked.
More cheers and laughs came from the crowd when she declared: 'Nobody f***s with the Queen.'
Hailing London as one of her favourite places, she said: 'It's so good to be back. Right back here where I belong. London has a very special place in my heart. When I was a young, young girl living in New York. I was a bartender in a restaurant. I robbed the cash register blind every night. Why? Because I was dying to come to London and check it out. So I saved up all my stolen cash and I came here and it was the most amazing experience of my life.'
Marking World Aids Day, the star paid tribute to her friends who have died from Aids and said the entire family of her adopted son died from the virus. 'We shall overcome one day,' she said.
Madonna plays one more night at the O2 before taking her show to Manchester, Birmingham and Glasgow.
From Press Association Via Yahoo! News