The purpose of this study is to determine the long-term relapse rate and associated risk factors in HBeAg-positive chronic hepatitis B (CHB) patients who had maintained virologic response (VR) for 1 year after lamivudine (LMV) discontinuation. We enrolled 55 treatment-naive HBeAg-positive CHB patients who achieved and maintained VR until 1 year after LMV discontinuation. Delayed relapse was defined as an elevation of HBV DNA after sustained VR for 1 year. During follow-up, 16 of 55 patients (29%) showed delayed relapse. Beginning 1 year after LMV discontinuation, the cumulative rates of relapse after 2 and 4 years were 29 and 44%, respectively. In multivariate analysis, age (P = 0.029) and >2,000 copies/ml HBV DNA 3 months after LMV discontinuation (P = 0.047) were significant predictors of delayed relapse. Delayed relapse is not infrequent, even in patients who maintain VR for 1 year after LMV discontinuation. Therefore, LMV maintenance therapy might be considered in HBeAg-positive CHB patients who achieve VR.