Voting, which began at 12:00 GMT on Friday, ends midday on Saturday.
Both the CSSD and ODS have laid out ambitious plans to put the struggling economy back on track in a campaign marked by a level of rivalry that has been largely absent during Fischer's rule.
The Social Democrats, led by Jiri Paroubek, a former prime minister, said it expects to restart economic growth by curbing corruption, luring investors with incentives and using money from European Union funds more efficiently.
The Civic Democrats, led by Petr Necas, has said it wants to turn things around by curbing government spending and keeping taxes low, and says it is planning to carry out pension and healthcare reforms.
Dubbed the "bulldozer" of Czech politics, Paroubek rose to international prominence in March last year when he triggered the no-confidence vote that toppled his arch-rival Topolanek.
The vote came at a critical time, with the Czech Republic holding the EU presidency.
Necas succeeded Topolanek as ODS leader in April after his predecessor was caught making offensive remarks about gays and Jews.
Experts have warned it could take months to form a government, with analysts saying the country needs fundamental reforms, including a pension system overhaul.
"We can't afford to waste time," David Marek, an analyst at Patria Finance in Prague, told the AP news agency.
The Czech economy contracted by 4.2 per cent last year, and the EU predicts growth of 1.6 per cent this year.
The budget deficit will likely reach 5.3 per cent in 2010, and the public debt is at a 35 per cent of gross domestic product, reasonable compared with other EU countries.