The two candidates in the run-off vote on Wednesday are current Prime Minister Branko Crvenkovski, seen as the favourite, and Sasko Kedev of the main opposition party, VMRO-DPMNE.
Voting started at 7am (0500 GMT), while polls were to close at 7pm (1700 GMT).
If less than 50% of 1.7 million eligible voters cast a ballot, the elections will be declared invalid and new polls would be organised.
But if enough voters come out, 41-year-old Crvenkovski, a veteran politician despite his age, seems to have the highest chance of winning the poll.
However, analysts would not exclude a possible surprise in the polls although Kedev, also 41, has almost no political experience. A heart surgeon by profession, he was first elected as a deputy in the Macedonian parliament in 2002.
The polls will be monitored by about 300 international observers. The first unofficial results are expected on Wednesday night.
However, there are fears that the turn-out in the vote, which comes after a first round held on 14 April, might not even reach the 50% mark required for the election to be considered valid.
A surprise result is not ruled out
The last opinion polls before the election showed Crvenkovski, who represents the ruling SDSM alliance, with 42.49% of voting intentions, and Kedev with 34.09%.
The surveys also indicated a possible turnout of between only 48 and 52%. About 55% of voters cast their ballot in the first round, less than in any election since the ethnically mixed republic broke away from the former Yugoslavia and became
independent in 1991.
Analysts said a successful turn-out and support from the 300,000-strong ethnic Albanian electorate might be decisive for the outcome of the run-off.
The Democratic Union for Integration (DUI), the ethnic Albanian grouping allied with the SDSM in Macedonia's ruling coalition, called on its supporters to come out and vote for Crvenkovski.
But the second-strongest ethnic Albanian party, the Democratic Party of Albanians (DPA), said it would not call on its supporters to vote for either of the candidates adding, however, it would not call for a boycott.