Michelle Obama told schoolchildren she was "thrilled to be back" on a visit to Oxford University today.
The US First Lady received a rapturous round of applause as she arrived at the world famous institution's Christ Church college.
Mrs Obama greeted pupils from Elizabeth Garrett Anderson (EGA) secondary school like old friends as she entered the college's dining room.
She first met pupils from the north London secondary school two years ago when she paid them a surprise visit during a trip to the capital with US president Barack Obama.
In a nod to Harry Potter - the dining room was used as the set for the Grand Hall at Hogwarts in the films - the school girls sat at two long tables to listen to Mrs Obama's remarks.
She told the youngsters: "How are you doing? It's good to see you again."
The 37 girls were specially picked for today's event because they are interested in science and are not reaching their full potential.
The meeting with Mrs Obama marked the culmination of a day of activities at the university for the youngsters, including campus tours, career discussions and mentoring sessions.
The trip, which was arranged at Mrs Obama's suggestion, has been designed to teach the girls about university and encourage them to think about studying for a degree.
Since visiting EGA in 2009, Mrs Obama has kept in touch with the school, writing letters and encouraging the girls in their studies.
Mrs Obama told the schoolgirls she worried about applying to top universities when she was young because of her background.
She said: "I remember back at a young age trying to decide what schools to apply to and how well-meaning but misguided people questioned whether someone with my background could succeed at an elite university.
"When I was accepted I had all kinds of worries and doubts.
"I wouldn't be as well prepared as students from privileged families and I wouldn't fit in.
"But after a few months away from home I realised I was just as capable and I had just as much to offer (as) any of my classmates."
In an inspiring speech, Mrs Obama, who wore a white jacket with a sparkling belt and black trousers, said: "We passionately believe that you have the talent within you, you have the drive, the experience to succeed at Oxford and universities just like it across the country and the world."
She told the youngsters that they have overcome challenges and hardships in their lives and that from these experiences they have learnt strength, courage and maturity.
Referring to her own experience of attending university, she said: "I realised if I worked hard enough, I could do just as well as anyone."
Success is not determined by background, but confidence and effort, she said.
Mrs Obama told the girls: "You have to work hard, you have to push yourself."