Liver biopsies are recommended to exclude significant liver inflammation in patients with chronic hepatitis B (CHB) with elevated HBV DNA but without other indications for antiviral treatment. We aimed to investigate the proportions and determinants of significant inflammation in Asian patients with CHB with detectable HBV DNA. We conducted a cross‐sectional study that retrospectively included 581 patients with CHB with detectable HBV DNA who had undergone liver biopsy. Liver inflammation and fibrosis were staged by Scheuer’s classification. Significant inflammation and significant fibrosis were defined as G ≥ 2 and S ≥ 2, respectively. There were 179 (30.8%) patients with alanine aminotransferase (ALT) < 1 × upper limit of normal (ULN), 205 (35.3%) patients with ALT 1‐2 × ULN, and 197 (33.9%) patients with ALT > 2 × ULN. A total of 397 (68.3%) patients had significant inflammation, and 340 (58.5%) patients had significant fibrosis. Significant inflammation was found in 85% of patients with significant fibrosis and in 44.8% of patients without significant fibrosis. Furthermore, 28.7% of patients with CHB with detectable HBV DNA and normal ALT in the absence of significant fibrosis had significant inflammation. Moderate HBV DNA (5‐7 log₁₀ IU/mL) was a risk factor for significant inflammation (odds ratio [OR] 6.929, 95% confidence interval [CI] 2.830‐16.966, P < 0.001) in patients with CHB with detectable HBV DNA, especially for patients with detectable HBV DNA and normal ALT in the absence of significant fibrosis (adjusted OR 13.161, 95% CI 1.026‐168.889, P = 0.048). Conclusion: A high proportion of CHB patients with detectable HBV DNA and normal ALT in the absence of significant fibrosis have significant liver inflammation. Liver biopsies are recommended to evaluate liver inflammation in such patients, especially for those with moderate HBV DNA.