We evaluated whether nucleos(t)ide analog (NA) influences the risk of non-hepatocellular carcinoma (non-HCC) malignancies in patients with chronic hepatitis B (CHB). A total of 9867 patients with CHB were followed up for ≥12 months for the occurrence of any type of malignancy between 1998 and 2013. Patients who received NA for ≥180 days were defined as the NA group. Propensity score matching produced the control (n = 2220) and NA groups (n = 2220) after adjustment for age, sex, and the presence of diabetes mellitus and liver cirrhosis. The National Health Insurance Service sample cohort dataset was used for external validation. Regarding non-HCC malignancies, only old age was an independent risk factor (>50 years; hazard ratio 3.17, 95% confidence interval 1.71-5.88, P < .001) in multivariate analysis. With regard to specific cancers such as thyroid, breast, lung, stomach, colorectal, pancreatobiliary, and hematologic malignancy, there was no difference of the incidence of each malignancy between the NA and control groups in both the hospital-based and external validation cohorts. NA treatment neither raises nor lowers the incidence of non-HCC malignancies in patients with CHB. Patients >50 years old are encouraged to undergo surveillance for malignancies similar to the general population.