Siena vs. Duke odds, prediction: 2026 NCAA Tournament picks from proven model

The 16th-seeded Siena Saints face the top-seeded Duke Blue Devils in the first round of the NCAA Tournament East Region on Thursday. Siena is coming off a 64-54 win over Merrimack in the Metro Atlantic Athletic Conference Tournament championship game on March 10, while Duke defeated Virginia 74-70 to win the Atlantic Coast Conference Tournament title on Saturday. The Saints (23-11), who have won four in a row, placed third in the MAAC regular-season standings with a 13-7 mark. The Blue Devils (32-2), who have won 11 straight, won the ACC regular-season title at 17-1 in league play. Duke will be without Caleb Foster (foot), while Patrick Ngongba II (foot) is questionable.

Tip-off from Bon Secours Wellness Arena in Greenville, S.C., is set for 2:50 p.m. ET. Duke leads the all-time series 1-0, earning a 92-74 win in 2015. Duke is a 28.5-point favorite in the latest Siena vs. Duke odds from DraftKings Sportsbook, while the over/under for total points scored is 135.5. Before making any Siena vs. Duke picks, check out the college basketball predictions from the SportsLine Projection Model.

The SportsLine Projection Model simulates every college basketball game 10,000 times. It entered the 2026 NCAA Tournament on a sizzling 11-1 run on top-ranked over/under picks dating back to last year, and is on a 28-22 run on top-rated CBB side picks. Anyone following could have seen HUGE returns!

The model has simulated Siena vs. Duke 10,000 times and the results are in. The model is going Over on the total, and it also says one side of the spread has all the value

So who wins Siena vs. Duke, and which side of the spread has all the value? Join SportsLine right now to see which side of the spread you need to jump on, all from the computer model that has simulated this matchup 10,000 times!