Background: Indication for de novo cardiac resynchronization therapy (CRT) has been recommended in mild heart failure (HF) patients with left ventricular (LV) ejection fraction (LVEF) < 50% and atrioventricular block (AVB). In contrast, the indication of CRT upgrade from right ventricular pacing (RVP) has been limited to severe HF patients with LVEF <35% and AVB. This study examined LV volumetric responses and clinical outcomes in mild HF patients with AVB who underwent CRT upgrade, compared with those of de novo CRT patients. Methods: This retrospective study focused on patients with CRT due to AVB, mild HF at New York Heart Association class II and LVEF < 50%. A total of 58 patients were divided into two groups: (1) 27 patients with CRT upgrade from RVP > 40% (Upgrade group, UG), and (2) 31 patients with de novo CRT implantation ( De novo group, DG). The echocardiographic assessment was performed at baseline and six months after CRT. The study endpoint was a combined endpoint with total mortality, HF hospitalization, or ventricular tachyarrhythmia events. Results: At six months after CRT, the LV end-systolic volume (LVESV) was significantly reduced in both groups (from 144.3 +/- 39.4 mL to 111.1 +/- 33.5 mL in UG, p < 0.01; from 134.5 +/- 36.6 mL to 123.5 +/- 45.6 mL in DG, p < 0.05); however, a significant improvement in LVEF was obtained in UG but not in DG (from 31.7 +/- 6.8% to 39.7 +/- 8.5% in UG, p < 0.01; from 34.2 +/- 7.3% to 36.0 +/- 9.7% in DG, p = 0.15). Consequently, the changes in LVESV and LVEF were significantly greater in UG than in DG. During the follow-up of 989 days, the survival rate for the composite events were similar between both groups ( p = 0.18). Conclusions: LV reverse remodeling was significantly greater in UG than DG, and the incidence of clinical composite events at mid-term follow-up was equivalent between UG and DG. CRT upgrade could be an acceptable indication in mild HF patients dependent on RVP. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Japanese College of Cardiology. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )