Thank you.

What time of night? And where?

Like 11PM or so, going from the East Village to 83rd and 2nd Avenue (or the nearest subway stop there). Thank you.

For that trip you'd be taking the 4, 5 or 6 (green lines). At any time they should be perfectly safe, but as always, use common sense. Don't flash money or jewelry and don't make aggressive eye contact with suspicious-looking people. I have been taking the subway by myself (I'm a not-intimidating-looking woman) for the past 10 years at all hours and have been fine so far, knock wood. And, finally, both those neighborhoods are full of younger people who will be out on the streets all night, so walking to and from stations you should feel totally comfortable as well.

I can confirm Anna's experience although I've ridden the route far less than she. I've ridden that train (4,5&6)
as late as 1AM and felt that it was perfectly safe.

Totally concur with above posters.