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Background: Our study aimed to evaluate the correlation between the sensitivity of adenosine deaminase (ADA) testing for the diagnosis of tuberculous peritonitis (TBP) and patient age or cirrhosis status. Methods: Clinical data for patients clinically diagnosed with TPB (n = 132) or not (n = 147) were assessed. ADA activity was compared among three age groups (< 45 yr, 45–60 yr, and ≥ 60 yr) and among cirrhosis-related subgroups. Cut-off values for the ADA test were analyzed among three patient populations (young non-cirrhotic, n = 97; older non-cirrhotic, n = 115; cirrhotic, n = 67), and validated in a cohort of 259 participants. Results: According to the multivariate regression analyses, age < 45 yr is highly predictive of TBP risk. The young non-cirrhotic TBP patients had higher ADA activity than the middle-aged or old controls (p < 0.01). Significantly decreased activity and efficacy of ADA were observed in the cirrhotic subgroup/population, regardless of age or cohort. For the above-mentioned two non-cirrhotic populations in the validation cohort, the ADA test showed excellent performance using thresholds of 30.5 IU/L and 20.5 IU/L, with respective sensitivities of 91.1% and 92.6%. Conclusions: ADA activity is negatively associated with increasing age and underlying cirrhosis. Optimizing cut-off values for the ADA test can increase its sensitivity in non-cirrhotic individuals older than 45 years.