Objectives The aim of this study was to evaluate whether clinical variables from the history, clinical presentation, and physical and neurological examinations of cats with vestibular syndrome were statistically predictive of the underlying diagnosis. Methods In total, 174 cats presenting with vestibular syndrome between January 2010 and May 2019 were investigated. Univariate statistical analysis of clinical variables was performed and those statistically associated with a diagnosis were retained for multivariable binary logistic regression modelling. Results The seven most prevalent diagnoses represented 95% of vestibular presentations, which included: otitis media/interna (n = 48), idiopathic vestibular syndrome (n = 39), intracranial neoplasia (n = 24), middle ear polyp (n = 17), feline infectious peritonitis (n = 13), thiamine deficiency (n = 13) and intracranial empyema (n = 11). Idiopathic vestibular syndrome was commonly associated with non-purebred cats and had 17.8 times the odds of an improving clinical progression (95% confidence interval [CI] 1.3–250.0; P = 0.03). Intracranial neoplasia was associated with older age and chronic onset of clinical signs, and was significantly more likely to have a central vestibular neuroanatomical localisation (95% CI 8.5–344349142.0; P = 0.015) with postural deficits on neurological examination. Thiamine deficiency was more common in female cats, with 52.6 times the odds of a waxing and waning clinical progression (95% CI 1.2–1000; P = 0.038) and 6.8 times the odds of presenting with bilateral vestibular signs (95% CI 1.0–45.7; P = 0.047) and wide excursions of the head (95% CI 1.0–45.7; P = 0.047). Middle ear polyps were associated with 8.8 times the odds of presenting with Horner syndrome (95% CI 1.5–50.0; P = 0.015). Conclusions and relevance Although it may be difficult to identify the underlying diagnosis in cats with vestibular syndrome from the presenting features alone, there are instances in which discrete clinical features may help to guide clinical reasoning when evaluating cats with vestibular presentations.