The 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) is formally qualified by the Food and Drug Administration as a valid patient-reported outcome measure for use in heart failure (HF) clinical trials. However, its length may increase respondent burden. The 12-item version (KCCQ-12) provides a more efficient alternative but was originally developed and validated in HF with reduced left ventricular ejection fraction (LVEF), and its performance relative to the KCCQ-23 has not been evaluated in HF with mildly reduced or preserved LVEF (HFmrEF/HFpEF). The purpose of this study is to examine the interchangeability of KCCQ-12 and KCCQ-23 in patients with HFmrEF/HFpEF. We conducted a participant-level pooled analysis of 4 randomized clinical trials (TOPCAT, PARAGON-HF, DELIVER, and FINEARTS-HF), including adults with HFmrEF/HFpEF. All trials collected the KCCQ-23 at baseline and follow-up visits. In this study, the KCCQ-12 overall summary scores (OSS) were derived from individual items of the KCCQ-23 OSS. Both scores ranged from 0 (worst) to 100 (best). We assessed concordance between KCCQ-12 OSS and KCCQ-23 OSS and compared prognostic discrimination and treatment-related changes. Of 18,216 participants (mean age: 72 ± 9 years; female: 46%; NYHA functional class II: 72%; mean LVEF: 55 ± 8%; median N-terminal pro-B-type natriuretic peptide levels: 987 [IQR: 517-1,781] pg/mL), baseline KCCQ-23 OSS was 65.5 ± 21.4, and KCCQ-12 OSS was 64.1 ± 21.7. Baseline KCCQ-12 OSS strongly correlated with KCCQ-23 OSS (Spearman ρ = 0.987), consistent across major subgroups and follow-up visits (all Spearman ρ > 0.980). Prognostic discrimination for cardiovascular death and HF hospitalization was comparable (C index: 0.583 for KCCQ-23 vs 0.586 for KCCQ-12). Treatment effects of HF drugs on KCCQ-OSS were similar across the 2 instruments in each trial and at each time point (all the differences between KCCQ-23 and KCCQ-12 were <1 point on a 0-100 scale). In patients with HFmrEF/HFpEF, the KCCQ-12 closely parallels the KCCQ-23, demonstrating comparable prognostic performance and treatment responsiveness. These findings support the KCCQ-12 as a lower-burden alternative for use in HF clinical trials. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist; NCT00094302; Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin Receptor Blocker Global Outcomes in HF with Preserved Ejection Fraction; NCT01920711; Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure; NCT03619213; Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure; NCT04435626).