The first thing you need to do is isolate whatever could be messing with your system. Make it as independent as possible. The fewer background processes, extra hardware and software, and even network traffic you can get, the better. Sometimes it's even a good idea to run these on a batch job that runs at night at a time when you know there's nothing else running.
The best statistical way that jumps in my mind is standard deviation. With a set of historical data, you should be able to acquire a mean and a stddev. If you get a result that is more than 3 or 6 stddevs from the mean (commonly known as 3-sigma or 6-sigma), you know you have something significantly different.
I'm sure you could simply pop the values in excel and get the stddev results.