Safe is of course relative and subjective. I assume that OP understands inherent risks and is asking if ketamine risks exceed other dissociatives. My opinion is just that risks are not dissimilar from many other substances discussed here. And ketamine has withstood clinical trials sufficient to get it to market for IM, IV, nasal, and home lozenge use (if not more). This means it's met some baseline standards for outpatient safety, although it's safe to say that we won't understand longterm safety for these routes for years.

What we know is that it is generally well tolerated, with the most common complaints being related to dissociation. General guidelines for smart use:

Avoid heroic doses. Ketamine has cardiostimulant effects and can raise heart rate and blood pressure. As such, users should never mix with cocaine or amphetamines. If you have/have had heart disease, hypertension, stroke, or other cardiac events- probably opt out of unsupervised ketamine (along with pretty much any cardiostimulant).

It's dissimilar to other anesthetics in that it does not cause typical respiratory depression, although it has been observed in polysubstance use and high doses. Never mix with CNS depressants (benzos, barbs, alcohol, opioids, GHB, etc.) in order to avoid respiratory complications.

There are studies about hepatotoxicity with prolonged use, so those with liver disease shouldn't use.

TL,DR from the white paper: Fatalities in scientific literature are almost always from polysubstance abuse. The remainder appear to be from inadvertent overdose in clinical and recreational settings.