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In HIV-negative cryptococcal meningoencephalitis, neurological deterioration can occur despite sterile follow-up cerebrospinal fluid (CSF) cultures, often due to postinfectious inflammatory response syndrome (PIIRS). A 37-year-old man presented with progressive headache, subacute ataxia, dysarthria and confusion. An MR scan of brain showed cerebellar-predominant T2/fluid-attenuated inversion recovery hyperintensities, leptomeningeal enhancement and acute microinfarcts. CSF showed elevated opening pressure, neutrophilic pleocytosis, low glucose and high protein. After confirming Cryptococcus neoformans, we started liposomal amphotericin B and flucytosine. Despite early improvement, he deteriorated around day 35 with sustained intracranial hypertension and progressive inflammation on imaging, yet with sterile follow-up cultures. We suspected PIIRS and gave intravenous methylprednisolone. He improved rapidly, with normalisation of CSF and intracranial pressure. Paradoxical worsening requires structured reassessment; confirming microbiological control allows targeted immunomodulation to reverse inflammatory injury.