Background: To determine if RV volume was predictive of survival and cardiovascular adverse event (CAE) after pulmonary valve replacement (PVR). Methods: We reviewed the MACHD (Mayo Adult Congenital Heart Disease) database for patients with tetralogy of Fallot (TOF) undergoing PVR, 2000–2015. The patients were divided into quartiles based on RV end-diastolic volume index (RVEDVI); those in the lowest quartile (Group A, n = 46) and the top quartile (Group B, n = 42) were selected as the study cohort. Results: In comparison to Group A, Group B patients were older at time of PVR (28 ± 4 vs 33 ± 5 years, P =.011) and had larger RV volumes (RVEDVI 127 [117–138] mL/m2 vs 1 91 [179–208], P <.001; RVESVI 64 [57–73] mL/m2 vs 122 [103–136], P <.001). A total of 28 CAE occurred in 23 patients during 69 (33–94) months follow-up: death (n = 4), heart transplant listing (n = 1), initiation of palliative care (n = 1), heart failure hospitalization (n = 11), stroke (n = 2) and sustained ventricular tachycardia/aborted sudden cardiac death (n = 9). Survival was similar between Groups A and B (95% vs 91% at 10 years, P =.273) but freedom from CAE was significantly lower in Group B (67% vs 36% at 10 years, P =.002). Combination of RVESVI: >95 mL/m2 and tricuspid annular plane systolic excursion/RV systolic pressure (TAPSE/RVSP) <0.4 predicted CAE with sensitivity of 67% and specificity of 92%. Conclusion: Patients undergoing PVR at larger RV volumes had similar survival but more overall CAE. A larger study population with a longer follow-up will be required to determine if early PVR provides survival benefit in the long-term.