There has been a lot of debate over whether a court should have to issue a specific search warrant just for a safe, or whether a search warrant for your property is enough to allow them to open such. The authorities always attempt to apply a search warrant for your house to mean your safe as well. You'd need some kind of pre-emptive action to try to stop that, and even then, good luck.
In the case of cryptography, if the contents are bad enough to put you in prison for a zillion years, obviously you have to make a judgment call as to the punishment if you refuse a court order to decrypt the contents. Since this is still such a relatively new gray area, I'd say a court would still blaze its own path (not depend primarily on prior precedent) in deciding if you're to be compelled. Perhaps you aren't likely to be convicted of the worst charges if you don't decrypt, and it might prevent the prosecution from building up other charges, but you will be punished by the court for refusing its order.
It'd have to be better than what is on the drive - assuming you've got anything on the drive to begin with (some kind of incriminating evidence or something else they can build charges with). The difference might very well be that you prevent the prosecution from building a strong enough case, and at the least maybe you buy yourself some time to build a better defense.
I'd predict that as major crime continues to shift to the digital realm, criminals will adopt ever stronger encryption for that very reason, and the government will use that practice to argue in favor of violating more civil rights. Seems to be the trend these days.
Like, the prosecution can't just say "we think he hid it on an encrypted HDD, but we aren't sure". The judge won't allow that. But if you claim to have forgotten the password, then the prosecution can speculate.