To assess the persistence of hepatitis G virus (HGV) infection and its association with liver disease, HGV RNA was assessed in the most recent serum sample for 246 long-term injecting drug users (IDUs) and in prior specimens for those found HGV RNA-positive. HGV RNA was detected at the most recent visit in 38 (15.4%). For 31 (82%), HGV RNA was also found at all prior visits occurring a median of 6.1 years earlier. HGV-positive IDUs were younger and had fewer years of drug use, suggesting that HGV RNA had previously been cleared. Serial samples from 29 short-term IDUs were then assessed. HGV RNA was detected in 9 (31%) of 29 short-term IDUs, and 5 (56%) of the 9 HGV infections cleared. No differences were detected in serum levels of liver-related enzymes among HGV RNA-positive and -negative participants (P > .20). HGV infection is not associated with hepatic inflammation. HGV clearance occurs after many acute infections but uncommonly in persons who remain RNA-positive years after exposure.