To have winners in any round, you must limit the mistakes in the Round of 64. If a Seed No. 4 wins the national
championship and your bracket had them being upset by a No. 13 seed, 630 of the 1920 points have been lost
(using the ESPN scoring system.) On the other hand, teams seeded No. 13 or lower have never reached the Final Four.
Let us look at each seed match-up in the Round of 64. All numbers reported are based on the 32 tournaments from 1985 to 2016.
No. 1 vs No. 16 : Yes, it will happen. Just as the Cubs finally won the World Series (it took 108 years), a No. 16 seed will win a game; no one knows just when it will happen. Given that over 40% of the teams in the Final Four are No. 1 seeds, pick all four No. 1 seeds to win.
No. 2 vs No. 15: Yes, this one happens, ocassionally. Only eight of the No. 15 seeds have won this game. For many years, the performance of the No. 15 seed looked similar to the No. 16 seed. However, since 2012, four No. 15 seeds won (out of 20 games played). Picking such a winner is tough. Moreover, the penalty for being wrong is enormous, given that over 22% of the teams in the Final Four are No. 2 seeds. Pick all four No. 2 seeds to win.
No. 3 vs No. 14, and No. 4 vs No. 13: These matchup are grouped together because of their similar records. No. 13 seeds are 26-102 and No. 14 seeds are 21-107. Yes, this one happens, and is highly likely to happen. In 28 of the past 32 tournaments, one of more of these seeds pulled a major upset. The penalty for being wrong is stiff, since 21% of the teams in the Final Four are No. 3 or No. 4 seeds. Moreover, only eight of the No. 13 or No. 14 seeds have ever reached the Sweet Sixteen, and all have lost that match-up. Pick zero or one of these teams to win.
No. 5 vs No. 12, No. 6 versus No. 11, and No. 7 versus No. 10: These matchup are also grouped together because of their similar records. No. 12 seeds are 46-82, No. 11 seeds are 46-82, No. 10 seeds are 50-78, resulting in a combined record of 142-242, or a 37% winning percentage. Moreover, atleast one No. 11 or No. 12 has won a game in every tournament. The combined record of the No. 11, No. 12, and No. 13 seeds in the round of 32 is 62-80, or a 44% winning percentage (better than their performance in the round of 64). They do fade in the Sweet Sixteen, with a record of 15-47, or a 24% winning percentage, with No. 10 seeds and No. 11 seeds getting 14 of these wins. No. 11 seeds have had the most staying power, reaching the Final Four three times. Picking one, two or three makes sense, with a slight preference for two. There will likely be more than this, but the price in picking too many and getting them wrong is too high.
No. 8 vs No. 9: The true toss up game. Since 1985, each seed has won 64 games. For many years, the No. 9 seeds had a slight advantage. More recently, the No. 8 seeds have done better. Flip a coin, or pick the more interesting mascot. Neither seed stays very long; only 17 of the 128 winners (since 1985) defeat the No. 1 seed in the Round of 32, which are fewer wins than the No. 10 seeds (23), the No. 11 seeds (19) or the No. 12 seeds (20) have in the Round of 32.
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