New interleukin (IL)-17A inhibitors seem to demonstrate smaller effects on tuberculosis (TB) reactivation than expected. To evaluate the risk of TB reactivation, to assess serial interferon (IFN)-γ levels, and to weigh up the risks and benefits of TB chemoprophylaxis in patients with psoriasis treated with IL-17A inhibitors. This dual-centre study included patients with psoriasis who were treated with IL-17A inhibitors. The incidence of active TB, serial IFN-γ levels tested by IFN-γ release assays (IGRAs), adverse events (AEs) and effectiveness were evaluated through 1 year in patients with psoriasis treated with IL-17A inhibitors. According to the chemoprophylaxis treatment regimen, patients with latent TB infection (LTBI) were classified into three groups: a complete chemoprophylaxis dose regimen (CCP), an incomplete chemoprophylaxis (ICCP) or no chemoprophylaxis (NCP). In 220 IGRA-negative patients, 17 of 220 (7.3%) became IGRA positive after receiving a mean of 69.1 weeks of IL-17A inhibitor treatment. Only one case of new-onset TB was observed after 52 weeks of ixekizumab therapy. Significant changes in IFN-γ levels were observed in IGRA-negative patients. Similarly, IFN-γ levels [listed as the mean (SD)] significantly increased at 1 year compared with baseline among IGRA-positive patients in the NCP [105 (68.7) vs. 236 (80.8) pg mL-1, P < 0.01] and ICCP [75.3 (48.3) vs. 608 (249) pg mL-1, P < 0.001] groups, whereas the changes were not significant [125 (26.6) vs. 131 (21.7) pg mL-1, P = 0.70] in the CCP group. During IL-17A inhibitor therapy, there is a need for increased awareness of annual screening and assessment of individual risk for early detection of TB infection. LTBI treatment is generally well tolerated and is effective in preventing increased IFN-γ responses in patients with psoriasis treated with IL-17A inhibitors.