Investigating risk factors for mpox’s infectious period is vital for preventing this emerging disease, yet evidence remains scarce. This study aimed to identify risk factors associated with the duration of mpox infectiousness among mpox cases in Vietnam. The primary outcome was the duration of the mpox infectiousness, defined between symptom onset and the first negative test result for the mpox virus. Fine and Gray’s regression models were employed to assess the associations between the infectious period and several risk factors while accounting for competing risks of death by mpox. Most mpox cases recovered within 30 days. Patients with HIV or treated at multiple facilities for mpox had lower incidence rates of cleared infection compared to those who were HIV-negative or treated at a single facility. In regression models, patients with mpox symptoms of rash or mucosal lesions (sub-distribution hazard ratios = 0.62, 95% confidence interval = 0.46–0.83), ulcers (0.57, 0.41–0.80), or fever (0.62, 0.46–0.83) had significantly prolonged infectious periods than those without such symptoms. Our findings provided insights for managing mpox cases, especially those vulnerable to prolonged infectious periods in settings with sporadic cases reported.