Objective To analyze the clinical characteristics of individuals with high hepatitis B virus (HBV) pregenomic RNA (pgRNA), and further explore the value of pgRNA in the management of patients with chronic hepatitis B. Methods From December 1st, 2020 to April 1st, 2022, chronic hepatitis B patients who had been treated with nucleotide analogues for a long time and followed up in the Hepatitis Clinic of the Center of Infectious Diseases, West China Hospital, Sichuan University were included, and the clinical characteristics of chronic hepatitis B patients with high pgRNA were analyzed and summarized. Results A total of 107 patients were included. Male patients accounted for 66.4%, with an average age of 44.02 years. There were no statistically significant differences in gender, age, aspartate transaminase, alanine transaminase, γ-glutamyl transferase, HBV surface antigen, proportion of patients with HBV e antigen ≥0.1 U/mL, HBV DNA, and alpha fetoprotein between the high and low pgRNA groups (P>0.05). The proportion of patients with HBV surface antigen<100 U/mL in the high pgRNA group was lower than that in the low pgRNA group (4.4% vs. 22.6%, P<0.05). Conclusion The proportion of chronic hepatitis B patients with high pgRNA whose HBV surface antigen≥100 U/mL is higher.