Background <p>Objective imaging biomarkers reflecting penile microvascular perfusion in erectile dysfunction are limited. Hounsfield unit measurements obtained from non-contrast computed tomography may offer a non-invasive approach to assess tissue perfusion. This retrospective cohort study evaluated the associations between penile and splenic tissue density values and erectile function scores, and explored their relationship with response to daily tadalafil therapy.</p> Results <p>A total of 194 men with erectile dysfunction who underwent non-contrast lower abdominal computed tomography were included. Tissue density values were measured in proximal, midshaft, and distal penile segments as well as in splenic parenchyma. Daily tadalafil 5 mg was associated with statistically significant improvements across erectile function domains (mean change in erectile function score: +7.9 points; p &lt; 0.0001). Baseline penile tissue density values demonstrated positive correlations with splenic tissue density, suggesting a potential association related to perfusion characteristics. Although responders exhibited lower baseline tissue density values in selected penile segments compared with non-responders, these parameters did not independently predict treatment response in multivariable analysis.</p> Conclusions <p>Computed tomography–derived tissue density measurements of penile and splenic tissues may offer complementary, objective information related to tissue perfusion in men with erectile dysfunction. While these findings support the exploratory use of imaging-based density analysis in understanding vascular and metabolic influences on erectile function, prospective multicentre studies with standardized protocols are required to validate their clinical utility.</p>