BACKGROUND: Systolic murmurs are common in adults without significant valvular heart disease (VHD) and are more prevalent in women than in men, but the determinants of murmur audibility remain unclear. We aimed to identify the physiological determinants of innocent murmurs and examine the basis for sex differences in murmur prevalence. METHODS: In this cross-sectional population-based study, we analysed data from 1680 participants in Tromsø7 without significant VHD who underwent echocardiography and heart sound recording. We used multivariable logistic regression with complete-case data from 1643 participants to identify determinants of innocent murmurs. RESULTS: Among 1680 participants, 339 (20.2%) had an innocent murmur. In multivariable analysis, mean aortic valve gradient was the strongest determinant (OR 23.79 per 5 mm Hg, 95% CI 15.01 to 38.71), followed by female sex (OR 3.42, 95% CI 2.38 to 4.99), age (OR 1.41 per 10 years, 95% CI 1.22 to 1.64), systolic blood pressure (OR 1.12 per 10 mm Hg, 95% CI 1.04 to 1.20) and haemoglobin (OR 0.86 per 10 g/L, 95% CI 0.75 to 0.98). Murmur probability increased steeply with increasing gradient and exceeded 50% at 6-8 mm Hg, depending on sex. Women had a higher murmur probability than men across the observed gradient range. CONCLUSIONS: In adults without significant VHD, systolic murmurs were strongly associated with mean aortic valve gradient and occurred at lower gradients in women than in men. These findings support interpreting systolic murmurs as a probabilistic and context-dependent clinical finding rather than a binary marker of VHD.