The clinical characteristics and outcomes in cryptococcal meningitis (CM) have been shown to vary depending on the underlying condition. The purpose of this study was to investigate these differences in patients with and without hepatitis B virus (HBV) infection. We performed a retrospective study at the Third Affiliated Hospital of Sun Yat-Sen University from January 2006 to June 2012. Thirty-two HBV-positive patients and 58 HBV-negative patients were included. Among the 90 patients with CM, 32 (35.6%) were HBV-infected. CM occurred in a younger population in the HBV-positive group, with a higher Charlson comorbidity score than the HBV-negative group. The HBV-positive group presented with lower initial complaints of visual symptoms, lower cerebrospinal fluid (CSF) white blood cell counts, lower percentages of the total protein in the CSF exceeding 0.45 g/l, higher glucose levels in the CSF, a higher percentage of positive results for Cryptococcus culture in the CSF, more extraneural involvement sites, and a higher proportion of normal brain images than the HBV-negative group. Factors for a poor prognosis in the HBV-positive group included liver cirrhosis and HBV DNA >10³ copies/ml. In the HBV-uninfected group, lower glucose in the CSF and hydrocephalus were the indicators of an unsatisfactory outcome. Certain clinical features of CM were found to be significantly different between HBV-infected and HBV-uninfected patients, including age and initial laboratory findings, as well as the indicators of an unsatisfactory outcome. Host defense defects in the HBV-infected group may lead to a lower intensity of inflammation in the pathogenesis of CM compared with the HBV-uninfected patients and may account for these divergences between the two groups. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.