She was introduced to tennis by her mother, Riana. She has two younger brothers, Oliver and Toby. Vaidišová follows the NHL, primarily supporting the Tampa Bay Lightning and enjoys reading, watching movies, yoga and bike riding. She likes pop music and is a fan of Madonna. She lists New York City as her favourite city because of its constant activity. Vaidišová speaks Czech, English, German and is studying French.
She became engaged to fellow Czech tennis player Radek Štěpánek, who is eleven years her senior, in late 2007. It has been suggested that the relationship was the cause of Vaidišová's decline in tennis. The two married on 17 July 2010 at Prague Castle.
An avid reader, Vaidišová is part of the "Get Caught Reading Campaign" to encourage people to read more. She has taken part in other philanthropic causes, such as becoming an ambassador for PlayPumps International, a non-profit organisation dedicated to bringing clean drinking water to African children.