General manager Ray Shero announced the operation after the Penguins' 5-3 preseason loss to the Columbus Blue Jackets.
He said Vokoun left the Saturday morning practice at CONSOL Energy Center after noticing swelling in his thigh. He was taken to a local emergency room, where doctors diagnosed the blood clot.
"The most important thing right now is Tomas' health and well-being," Shero said. "The clot was dissolved by the procedure, and the doctors tell us that he will remain in the hospital for several days. We will continue to monitor his progress after that."
Penguins team physician Christopher Harner said there was no injury that led to the clot.
The 37-year-old Vokoun played 20 regular-season games for the Penguins in 2012-13, going 13-4 with a 2.45 goals-against average. He also appeared in 11 playoff games and was 6-5 with a 2.10 GAA.
The native of Karlovy Vary in the Czech Republic has played 15 NHL seasons with Montreal, Nashville, Florida, Washington and the Penguins.
Jeff Zatkoff is likely to be the Penguins' backup goalie in Vokoun's absence.