The vote is a test not only for the country of around 1.6 million people, but for a region worried at the retreat of democracy after coups in Guinea and Mauritania and a deepening political crisis in Niger.
"The real test for Guinea-Bissau is not whether the election is held peacefully, but whether state institutions have the capacity to prevent the country from sliding into chaos in the aftermath," said Kissy Agyeman-Togobo of IHS Global Insight.
"The military has been far too dominant in Bissau-Guinean politics to date, so there is a real need for the international community to offer support for capacity building."
'Peace and justice'
The three front-runners all pledge peace and justice.
The biggest party in parliament, the PAIGC, is represented by Malam Bacai Sanha, interim president from 1999-2000 after a coup and brief civil war.
Former President Koumba Yala, overthrown in a 2003 coup, is also expected to do well. The former philosophy professor has the backing of the biggest tribe, the Balante.
Henrique Pereira Rosa, standing as an independent, served as interim president between the overthrow of Yalla and the 2005 election won by Vieira.
If no candidate wins an outright victory in the ballot, a second round will be held.