The incidence of hepatocellular carcinoma (HCC) was recently reported to be lower in Asian chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) than entecavir (ETV), but this finding remains controversial. We assessed whether there was a difference between ETV and TDF treated patients of the well monitored, multicenter European PAGE-B cohort in the HCC incidence and other patient outcomes.We included 1935 Caucasians with CHB, with or without compensated cirrhosis, treated with ETV (n=772) or TDF (n=1163) monotherapy. Mean follow-up has been 7.1±3.0 years from ETV/TDF onset.The 5-year cumulative HCC incidence was 5.4% in ETV and 6.0% in TDF treated patients (log-rank, P=0.321) without significant difference in any patient subgroup [with or without cirrhosis, naive or experienced to oral antiviral(s) (total, with or without cirrhosis)]. In multivariable Cox regression analyses, the hazard of HCC was similar between ETV and TDF treated patients after adjustment for several HCC risk factors. ETV and TDF treated patients had similar rates of on-therapy biochemical and virological remission, HBsAg loss, liver transplantation and/or death. Elastographic reversion of cirrhosis at year 5 (liver stiffness <12 kPa) was observed in 245/347 (70.6%) patients with pretreatment cirrhosis being more frequent in TDF than ETV treated patients (73.8% vs 61.5%, P=0.038).In Caucasian CHB patients, with or without cirrhosis, ETV and TDF long-term monotherapy is associated with similar HCC risk and rates of biochemical and virological remission, HBsAg loss and liver transplantation or death, but TDF seems to result in more frequent elastographic reversion of cirrhosis at year 5.