The 46-year-old was married for 10 years to fellow actor Dennis Quaid, 54, until she had an affair with co-star Russell Crowe during filming of 2000 movie Proof of Life.
The actress told Hello! magazine that she found it impossible to maintain a romantic life with the constant demands of her work.
She said: “It’s very difficult to be a career person and have a relationship. I didn’t succeed at doing it at all. It’s incredibly hard.”
She added: “I think you have to figure out some way of keeping all of those capabilities and requirement in your life in balance.”
While her own relationships failed Miss Ryan built a career starring in romantic films in which love conquers all – including You’ve Got Mail, Sleepless in Seattle and When Harry Met Sally.
The Golden Globe winner admitted that it was difficult to leave her relationship with Crowe behind after news of the affair became public.
She said in 2006: “Russell was incredibly gracious to me during a really hard time and in the aftermath.
“I empowered myself by not staying in the thing with Russell. I felt it was going to be repeating some similar patterns that I’d just gotten out of and it was a drag because I was crazy about him.”
She has insisted that her marriage was no longer working when the co-stars became involved.
She told the Oprah Winfrey show: “Russell wasn’t a homewrecker.
“He didn’t talk and I’ll always be grateful to him for that. But I did not leave my marriage for him. I left because it was not working.”
The actress claimed she has mellowed since she passed 40 and adopted three year-old Daisy True from China two years ago. She also has a 15 year-old son, Jack Henry, from her relationship with Quaid.
She added that turning 40 made no real difference to her life.
She said: “I just don’t feel like it’s seminal or major in any way. I like my life right now, I really like it. Whatever it’s taken to get here, I appreciate.”
Despite her chequered love life she insisted she still “absolutely, absolutely” believes in romance.
Miss Ryan is not the only woman in Hollywood whose relationships have cracked under the pressure of work and fame.
Bridget Jones actress Renee Zellweger, 39, has had a succession of high profile failed relationships including Jim Carey and White Stripes musician Jack White as well as a brief seven-month marriage to country singer Kenny Chesney, which was annulled in December 2005.
Gwyneth Paltrow, 35, struggled to settle down after her engagement to Brad Pitt ended in 1997. As her acting career went from strength to strength she was linked to actors Ben Affleck, Luke Wilson, Chris Heinz and Robert Sean Leonard.
Since her marriage to Chris Martin in 2003 she took an extended break from the film industry to have her two children Apple, four, and Moses, two.
After her marriage to Tom Cruise ended in 2001 41 year-old Nicole Kidman’s career took off and she was named the highest paid Hollywood actress in 2006. But her personal life was more chequered after she was linked with Robbie Williams, Adrien Brody and rocker Lenny Kravitz.
She married country singer Keith Urban in 2006 and gave birth to daughter Sunday Rose last month.
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