OBJECTIVES: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a patient-reported outcome measure assessing symptoms, functional impacts, and health-related quality of life in patients with heart failure. Symptoms and presentation of heart failure may differ for men and women, raising the possibility that men and women interpret questions and respond differently, potentially introducing measurement bias. This study explored potential differential item functioning (DIF) between men and women responding to the KCCQ. METHODS: Data were from the HF-ACTION trial, a multicenter, randomized controlled trial of exercise training in chronic heart failure patients with reduced ejection fraction (n = 1670 men; n = 661 women). DIF tests included the item response theory (IRT)-based Wald test and ordinal logistic regression (OLR). Both methods evaluate how men and women respond to each KCCQ item after adjusting for their health status/quality of life using other items in the KCCQ. The magnitude of gender DIF on the KCCQ domain scores was examined using IRT characteristic curves by gender, and the weighted area between the expected score curves (wABC). For DIF identified using OLR, the pseudo-r² method provided insight on magnitude of DIF by quantifying differences in fit with and without interactions by gender. RESULTS: Four KCCQ items [Swelling frequency, Swelling burden, Shortness of breath frequency, and Intimate relationships with loved ones] exhibited statistically-significant DIF by gender (p < 0.01), but the magnitude was generally small (wABC: 0.09-0.66; pseudo-R² difference: 0.00-0.02) and the overall impact on KCCQ domain scores was minimal. CONCLUSIONS: Though we identified statistically-significant DIF by gender for some KCCQ items, the magnitude of the bias appears small for KCCQ domain scores, suggesting similar representations of heart failure concepts in men and women.