The runup to the election has been marred by violence, with more than 100 fatalities reported from politically motivated bombings since early April.
Just hours after voting started, twin bomb blasts in the port city of Karachi left 10 people dead and 30 others wounded.
The explosions targeted the political offices of the Awami National Party, one of three secular liberal parties that have been targeted by Taliban militants.
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The Taliban considers the election un-Islamic and had threatened to carry out suicide attacks.
Other violence on Saturday:
- In the northwestern city of Peshawar a bomb attached to a motorcycle exploded outside a polling station, killing a boy and wounding 10 other people.
- In the southwestern Baluchistan province where separatists oppose the election, gunmen killed two people outside a polling station in the town of Sorab, police official Mohammed Yousuf said.
- Also in Baluchistan, a shootout between supporters of two candidates in the town of Chaman ended with four people dead, said Ismail Ibrahim, a government official.
There are some 600,000 security and army personnel stationed at polling stations around the country.
Before polls opened, Pakistan's borders with Iran and Afghanistan were sealed in an attempt to keep foreign militants out.
The frontrunners in the election are the Pakistan Muslim League led by the former prime minister Nawaz Shariff and The Movement for Justice Party led by the former cricket star Imran Khan.
While twice-elected Sharif has billed himself as the candidate of experience, Khan is trying to tap into the frustrations of millions of Pakistanis who want a change from the traditional politicians who have dominated Pakistani politics for years.
Khan's mythical status grew even larger this week after he survived a horrific fall off a forklift during a campaign event in the eastern city of Lahore that sent him to the hospital with three broken vertebrae and a broken rib. He was not expected to vote Saturday because he can't travel to his polling place.Suggest a correction