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This study aimed to reveal characteristics and clinical relevance of HBV intergenotypic recombinants. Serum samples of 516 patients from Northern China were collected, including 131 with acute hepatitis B (AHB), 239 with chronic hepatitis B (CHB), and 146 with acute-on-chronic liver failure (ACLF). Full-length HBV genomes were sequenced and HBV genotypes were analyzed. Genotypes C, B, D, and intergenotypic recombinants were detected in 71.12% (367/516), 19.96% (103/516), 0.78% (4/516), and 8.14% (42/516) of the patients. The latter comprised 21 with AHB, 10 with CHB, and 11 with ACLF; and the occupations of intergenotypic recombinants in AHB, CHB, and ACLF groups were 16.03%, 4.18%, and 7.53% (P 0.01), respectively. HBV B/C and C/D hybrids accounted for 85.71% (36/42) and 14.29% (6/42) of the intergenotypic recombinants. In AHB and CHB groups, serum HBV DNA levels were significantly lower in patients with intergenotypic recombinants than those without intergenotypic recombinants. Difference in basal core promoter A1762T/G1764A mutations and precore G1896A mutation incidences was not significant between B/C recombinant and genotypes B or C virus, although the significance was there between genotypes B and C viruses. Clonal sequence analysis showed that intergenotypic recombinant viral strains existed in single or in concomitance with other genotype virus. Phenotypic analysis showed that viral replication capacity was similar between recombinant and non-recombinant strains in tested samples. Taken together, the occurrence of intergenotypic recombinant HBV is relatively low in HBV-infected patients in Northern China, and intergenotypic recombinant HBV infection is likely favorable to induce an acute course of disease. J. Med. Virol. 89:139-145, 2017. © 2016 Wiley Periodicals, Inc.