O'Leary made her name in mountaineering in 2004, when she became the first Irish woman to reach the summit of Mount Everest, having failed on her first attempt in 2003 due to gastroenteritis. She climbed as a member of the Wyeth Irish Everest Expedition, led by Pat Falvey. She also became the first Irish woman to ascend the Himalayan peak Ama Dablam and to climb the Seven Summits—the highest mountains on each continent. In 2008, O'Leary joined the Beyond Endurance expedition led by Falvey to the South Pole, making her the first woman to successfully ski to the South Pole.