The Masculinity in Chronic Disease Inventory (MCD-I) is a new measure of internalized masculine beliefs previously validated in the context of prostate cancer. The present study assessed the validity of the MCD-I in men with other chronic diseases to explore its potential for wider application. A cross-sectional survey of 633 men aged 47–93 years old (M = 68 years), of whom 68% reported ≥2 chronic conditions, was conducted. Measures included the MCD-I and Erectile Function. Exploratory and confirmatory factor analyses were performed followed by tests for discriminant validity. A five-factor structure was confirmed that explained 60% of the variance, with good to excellent reliabilities (α = 0.68–0.93) for the domains of Optimistic Action, Sexual Importance/Priority, Family Responsibilities, Emotional Self-Reliance, and Strength/Fitness. The MCD-I is a valid measure of internalized masculine beliefs for men with chronic disease that appears sensitive to age and to sexual health. The tailoring of health services for men can be guided by MCD-I outcomes to ensure gender-sensitized men’s health interventions.