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Which is appropriate?

One of the most significant adversities that (have or has) affected me was …

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    "Have" goes with plural, and "has" with singular. Adversity has, adversities have. But "one of the most significant adversities" is singular, thus "has."
    – developerwjk
    Commented Oct 8, 2013 at 22:44

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Both are correct. The difference is very clear, though it generally doesn't strike at once. Think again.

One of the most significant adversities that have affected me was …

(Many adversities affected me, one of them was …)

One of the most significant adversities that has affected me was …

(There were many adversities, one of them that affected me was …)

One of the most significant adversities that affected me was …

is another possibility.

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I would say "have", the subject being "things", and then "was", the subject being "one".

Otherwise, "many things" would be connected to nothing and left dangling.

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