BACKGROUND: Diabetes mellitus (DM) increases tuberculosis (TB) risk. We assessed the prevalence of hyperglycemia (DM and impaired glucose regulation [IGR]) in persons with TB and the association between hyperglycemia and TB at enrollment and 3 months after TB treatment in the context of human immunodeficiency virus (HIV) infection. METHODS: Adults presenting at a Cape Town TB clinic were enrolled. TB cases were defined by South African guidelines, while non-TB participants were those who presented with respiratory symptoms, negative TB tests, and resolution of symptoms 3 months later without TB treatment. HIV status was ascertained through medical records or HIV testing. All participants were screened for DM using glycated hemoglobin and fasting plasma glucose at TB treatment and after 3 months. The association between TB and DM was assessed. RESULTS: Overall DM prevalence was 11.9% (95% confidence interval [CI], 9.1%-15.4%) at enrollment and 9.3% (95% CI, 6.4%-13%) at follow-up; IGR prevalence was 46.9% (95% CI, 42.2%-51.8%) and 21.5% (95% CI, 16.9%-26.3%) at enrollment and follow-up. TB/DM association was significant at enrollment (odds ratio [OR], 2.41 [95% CI, 1.3-4.3]) and follow-up (OR, 3.3 [95% CI, 1.5-7.3]), whereas TB/IGR association was only positive at enrollment (OR, 2.3 [95% CI, 1.6-3.3]). The TB/DM association was significant at enrollment in both new and preexisting DM, but only persisted at follow-up in preexisting DM in patients with HIV-1 infection. CONCLUSIONS: Our study demonstrated high prevalence of transient hyperglycemia and a significant TB/DM and TB/IGR association at enrollment in newly diagnosed DM, but persistent hyperglycemia and TB/DM association in patients with HIV-1 infection and preexisting DM, despite TB therapy.