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The Blue Devils gave up 30 unanswered points after taking a 14-10 lead and end the 2016 season with a 4-8 record.
The Duke defense allowed several big plays in the passing game that broke Saturday's game open. Miami quarterback Brad Kaaya finished with 396 yards and four touchdowns.
The Blue Devils had no answer for Miami's offense after halftime.
Both of David Njoku's catches Saturday for Miami were touchdowns that went for more than 50 yards.
Head coach David Cutcliffe's team got blown out twice to end the 2016 regular season after a slew of injuries decimated Duke's defense.