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Background: As a standard, significant pleural effusion, whether tuberculous (TB) or not, requires therapeutic thoracocentesis. We tested the hypothesis that standard anti-TB chemotherapy alone can resolve significant pleural effusion.Methods: 20 eligible patients with TB pleural effusion of at least 30% of the hemithorax (10 with moderate-size and 10 with large-size effusion, respectively) were retrospectively reviewed for radiological resolution of their effusions at two, six and 12 months after commencement of standard six-month therapy.Results: The mean percentage resolutions in both groups were comparable (48% vs 46% at two months; 59% vs 85% at six months; 84% vs 95% at 12 months). The mean sizes of effusions were also comparable (18% vs 33% at two months; 14% vs 10% at six months; 6% vs 4% at 12 months). Cigarette smoking and Indian ethnicity were univariately associated with incomplete resolution of effusions.Conclusion: Standard anti-TB chemotherapy alone appears to be sufficient to resolve significant TB pleural effusion. An avoidance of therapeutic thoracocentesis may reduce the risk of infection exposure or allow better channelling of resources in certain clinical settings.