If it works, the interceptor will smash into a dummy warhead carried by the ICBM at 15,000 miles an hour - one speeding bullet hitting another.
It worked last October, but it was not a realistic test of an actual missile attack.
Even so, there were technical glitches that critics say raise questions about the reliability of a national missile defense, which would have to work perfectly in order to protect the U.S. from incoming missiles armed with nuclear, chemical or biological warheads.
If it is ever deployed, the system will consist of 100 interceptor missiles, enough to protect the U.S. from a small-scale missile attack by a rogue state like North Korea or Iraq.
The Pentagon had originally planned to spend $10 billion to build the system, but this year's budget calls for an extra $2 billion, a 20% increase in just 1 year.
The Clinton administration is expected to decide this summer whether to begin building the system and this latest test will go a long way toward determining the outcome of that decision.