Financial barriers are a key limitation to accessing health services, such as tuberculosis (TB) care in resource-poor settings. In Ghana, the National Health Insurance Scheme (NHIS), established in 2003, officially offers free TB care to those enrolled. Using data from the first Ghana's national TB patient cost survey, we address two key questions 1) what are the key determinants of costs and affordability for TB-affected households, and 2) what would be the impact on costs for TB-affected households of expanding NHIS to all TB patients? We reported the level of direct and indirect costs, the proportion of TB-affected households experiencing catastrophic costs (defined as total TB-related costs, i.e., direct and indirect, exceeding 20% of their estimated pre-diagnosis annual household income), and potential determinants of costs, stratified by insurance status. Regression models were used to determine drivers of costs and affordability. The effect of enrolment into NHIS on costs was investigated through Inverse Probability of Treatment Weighting Analysis. Higher levels of education and income, a bigger household size and an multi-drug resistant TB diagnosis were associated with higher direct costs. Being in a low wealth quintile, living in an urban setting, losing one's job and having MDR-TB increased the odds of experiencing catastrophic costs. There was no evidence to suggest that enrolment in NHIS defrayed medical, non-medical, or total costs, nor mitigated income loss. Even if we expanded NHIS to all TB patients, the analyses suggest no evidence for any impact of insurance on medical cost, income loss, or total cost. An expansion of the NHIS programme will not relieve the financial burden for TB-affected households. Social protection schemes require enhancement if they are to protect TB patients from financial catastrophe.