<ns4:p><ns4:bold><ns4:italic>Background:</ns4:italic></ns4:bold><ns4:italic />Patients with tuberculosis (TB) symptoms in low-resource settings face convoluted diagnostic and treatment linkage pathways, incurring substantial health-seeking costs. In the context of a randomised trial looking at the impact of novel diagnostics such as computer-aided chest x-ray diagnosis (CAD4TB), we aimed to investigate the costs incurred by patients seeking TB diagnosis and whether optimised diagnostic interventions could result in a reduction in the cost faced by households.</ns4:p><ns4:p><ns4:bold><ns4:italic>Methods:</ns4:italic></ns4:bold>PROSPECT was a three-arm randomised trial conducted in a public primary health clinic in Blantyre, Malawi during 2018-2019 (trial arms: standard of care [SOC]; HIV testing [HIV]; HIV testing and CAD4TB [HIV/TB]). The direct and indirect costs incurred by 219 PROSPECT participants over the 56-day follow-up period were collected. Costs were deemed catastrophic if they exceeded 20% of annual household income. We compared mean costs and used generalised linear regression models to examine whether the interventions could result in a reduction in total costs.</ns4:p><ns4:p><ns4:bold><ns4:italic>Results:</ns4:italic></ns4:bold><ns4:italic />The mean total cost incurred by all 219 participants was US$12.11 (standard error (SE): 1.86). The indirect and direct cost was US$8.47 (SE: 1.66) and US$3.64 (SE: 0.38), respectively. The mean total cost composed of 5.6% of the average annual household income. In total, 5% (9/180) of the participants with complete income data incurred catastrophic costs. Compared to SOC, there was no statistically significant difference in the mean total cost faced by those in the HIV (ratio: 0.77, 95% CI: 0.51, 1.19) and HIV/TB arms (ratio: 0.85, 95% CI: 0.53, 1.37).</ns4:p><ns4:p><ns4:bold><ns4:italic>Conclusions:</ns4:italic></ns4:bold><ns4:italic />Despite the absence of user fees, patients seeking healthcare with TB symptoms incurred catastrophic costs. The optimised TB diagnostic interventions that were investigated in the PROSPECT study did not significantly reduce costs. TB diagnosis interventions should be implemented alongside social protection policies whilst ensuring healthcare facilities are accessible by the poor.</ns4:p>