PURPOSE: Genital Herpes Simplex Virus-2 (HSV-2) epidemic is highly active worldwide and can be associated with severe morbidity and mortality. This study aimed to estimate the prevalence and incidence of HSV-2 infection among a vulnerable population of active heroin injectors in Hai Phong, Vietnam, and identify associated risk factors. METHOD: Associations between HSV-2 infection and socio-demographic characteristics and sexual behaviors were explored in a univariable analysis of seroprevalence. Risk factors were defined using a multivariable Poisson regression accounting for time of follow-up. RESULTS: HSV-2 seroprevalence at baseline was 20.8% [95%CI: 17.8-22.2] for the 1281 men people who inject drugs (PWID), and 67.4% [95%CI: 60.1-74.1] for the 184 women PWID. For HSV-2 incidence, we accumulated a follow-up time of 1156.0 and 85.9 years for men and women, respectively. Standardised incidence rate was 4 [95%CI: 2.2-7.5] and 17.5 [95%CI: 5.7-53.8] infections per 100 person-years for men and women, respectively. Factors independently associated with HSV-2 seroconversion were HIV and injecting drug use for 5-10 years for men, and declared an uncontrolled HIV viral load and the use of street methadone. CONCLUSION: High HSV-2 prevalence and incidence among PWID in Hai Phong point out the burden of sexually transmissible infections in this population. Together these results advocate for a reinforcement of HSV-2 care and prevention in this population and identify PWID as future beneficiaries of upcoming therapeutic/prophylactic vaccines.