A cross-sectional study was carried out in injecting drug users (IDUs) from Greece to assess the seroprevalence of human herpesvirus 8 (HHV-8) and to identify potentially associated risk factors. A total of 288 IDUs were tested for K8.1 antibodies to HHV-8 lytic antigen. Associations between HHV-8 serostatus and potential risk factors were examined using univariate and multivariate logistic regression analysis. Seroprevalence of HHV-8 was 24.3% (95% CI 19.5-29.7), increasing with age from 19.4% in those aged <30 years to 52.9% in those aged 40 years (P for trend=0.003). No statistically significant associations between HHV-8-positive status and gender, educational level, age at first drug injection, needle sharing, number of imprisonments, complications from drug overdose, HIV and HCV were observed. In the multivariate logistic regression analysis, older age (40 vs. <40 years, OR 3.30, 95% CI 1.14-9.56) and report of septicaemia/abscess (yes vs. no, OR 1.80, 95% CI 1.01-3.18) were each independently associated with higher HHV-8 seroprevalence. HHV-8 is highly prevalent in the IDU population in Greece. The independent association between HHV-8 and reported abscess or septicaemia supports the hypothesis that poor hygiene conditions in the setting of drug injection may contribute to HHV-8 transmission.