Despite heavy rainfall in the capital, Bissau, most polling stations opened on time, at 7:00 am. Election observers say turnout was a little lower than expected in Bissau because of the weather, but outside the capital, turnout was high.
There were no reports of violence, and lines outside polling stations were kept in order by uniformed police.
Voters have been eager to cast their ballots in hopes of bringing stability to the turbulent former Portuguese colony of 1.4 million people.
One voter, standing in line outside a polling station in Bissau, said she braved the rain because she is worried about the country's future.
She says she is concerned about the outcome of the election in Guinea-Bissau. She fears that neither candidate will agree with the final results.
The two contenders are ruling party candidate Malam Bacai Sanha, who won most votes in June's first round of voting, and former military ruler Joao Bernardo Vieira.
Both candidates have pledged to end years of political instability in Guinea-Bissau, which is one of the world's poorest countries.
Another former president, Kumba Yala, who was ousted in a 2003 coup, failed to win enough votes to make the run-off. He tried to contest the first-round results, and was asked by the government to back down. He then asked his supporters from the Social Renovation Party to vote for Mr. Vieira, who is running as an independent.
Mr. Sahna cast his vote in the capital, telling a crowd gathered at the polling station he was confident of victory. He said his party will bring peace and stability, as it had done in the past.
Mr. Vieira seized power in a coup in 1980, won elections in 1994, but was ousted in a coup in 1999. Mr. Sahna took over as a transitional president after the coup against Mr. Vieira.
Analysts say loyalties of the divided army will be crucial in the months following the election.