How to define a VB.NET DataTable Column as primary key after creation

As long as the values in the column are unique

table.PrimaryKey = new DataColumn[] { table.Columns["Id"] };

adjust for your column names.

Here is a one-liner in VB (the question was with "using VB.NET"). This example is with 2 columns indexed:

table.PrimaryKey = New DataColumn() {table.Columns("column1"), _
                                     table.Columns("column2")}

Update: And here's another one-liner on how to use this 2 columns index to find a row:

table.Rows.Find(New Object() {value1, value2}) '<- DataRow returned

Update 2: And the complete example how to find a row using primary keys with a DataTable already filled with data:

'Define primary keys (you do this only once)
table.PrimaryKey = New DataColumn() {table.Columns("column1"), _
                                     table.Columns("column2")}
'Find a row:
Dim MyDataRow As DataRow
MyDataRow = table.Rows.Find(New Object() {value1, value2}) '<- DataRow returned
If MyDataRow IsNot Nothing Then 'If a row is found
    Return MyDataRow.Item("column3")
End If