Background The International Index of Erectile Function (IIEF) stands out for its utility and widespread use to measure sexual function in men. However, it lacks consistency in its internal latent structure across studies, has not been evaluated for measurement invariance, and has not undergone psychometric validation for its 15-item form in Spanish among South American countries.Aim To examine the IIEF's psychometric evidence (ie, structural/criterion validity and reliability) in a sample of adult men and determine its measurement invariance across relationship status (single vs in a relationship) and age generations (generations Z, Y/millennials, and X).Methods A sample of 650 sexually active males was derived from a broader Chilean study (Chilean Sex and Sexuality Study). We used a confirmatory factor analysis to determine the IIEF's structural validity, sexual satisfaction dimensions to establish its criterion-related validity, and Cronbach alpha and McDonald omega to assess the reliability of its scores.Outcomes Measures of goodness of fit.Results The evidence supported the 5-factor latent solution. Meanwhile, criterion-related validity revealed subtle yet significant differences in sexual satisfaction, with younger men displaying higher satisfaction in various sexual domains. In contrast, middle-aged men and those in a relationship showed better sexual function. Finally, the IIEF was invariant across age groups and relationship status at the factor covariance level.Clinical Translation This study provides evidence that the IIEF is a valid, reliable, and invariant tool for the clinical practice in men's sexual health, particularly that associated with their sexual function and dysfunction.Strengths and Limitations The study included a comprehensive validity analysis of the IIEF's psychometric properties, demonstrating its reliability and validity across diverse Chilean male subpopulations. The study also offered the IIEF's first assessment of measurement invariance and confirmed its suitability for clinical and research use in the Chilean population. Meanwhile, the study's limitations include a lack of clinical population and a sample predominantly younger, cisgender, and heterosexual.Conclusion Our study provides evidence of the IIEF's 5-factor structure and measurement invariance across age generations and relationship status in Chilean men, supporting its validity for clinical use and research and broadening its applicability in global sexual health studies, particularly in the Spanish-speaking South American male population.