BackgroundThe incidence of cryptococcal meningitis (CM) and tuberculous meningitis (TBM) have gradually increased in recent years. These two types of meningitis are easily misdiagnosed which leads to a poor prognosis. In this study we compared differences of clinical features and prognostic factors in non-HIV adults with CM and TBM.MethodsWe retrospectively reviewed the medical records of CM and TBM patients from January 2008 to December 2015 in our university hospital in China. The data included demographic characteristics, laboratory results, imaging findings, clinical outcomes.ResultsA total of 126 CM and 105 TBM patients were included. CM patients were more likely to present with headache, abnormal vision and hearing, and they might be less prone to fever and cough than TBM patients (P < 0.05). Higher percentage of CM patients presented with cerebral ischemia/infarction and demyelination in brain MRI than TBM patients (P < 0.05). CM patients had lower counts of WBC in CSF, lower total protein in CSF and serum CD4/CD8 ratio than TBM patients (P < 0.05). After three months of treatment, CM group have worse outcome than TBM group (P < 0.05). Multivariate analysis showed that age more than 60y (OR = 4.981, 95% CI: 1.955–12.692, P = 0.001), altered mentation (OR = 5.054, 95% CI: 1.592–16.046, P = 0.006), CD4/CD8 ratios < 1 (OR = 8.782, 95% CI: 2.436–31.661, P = 0.001) and CSF CrAg ≥ 1:1024 (OR = 4.853, 95% CI: 1.377–17.098, P = 0.014) were independent risk factors for poor prognosis for CM patients. For TBM patients, hydrocephalus (OR = 7.290, 95% CI: 1.630–32.606, P = 0.009) and no less than three underlying diseases (OR = 6.899, 95% CI: 1.766–26.949, P = 0.005) were independent risk factors, headache was a protective factor of prognosis.ConclusionsOur study provided some helpful clues in the differential diagnosis of non-HIV patients with CM or TBM and identified some risk factors for the poor prognosis of these two meningitis which could help to improve the treatment outcome. Further studies are worth to be done.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2126-6) contains supplementary material, which is available to authorized users.