Purpose: We aimed to examine if same-sex partnership in men is associated with cardiovascular disease (CVD) and whether this relationship can be explained by accumulated risk factors in late adolescence using causal mediation analysis. Methods: All men born in Sweden between 1952 and 1956, who participated in mandatory Swedish military service conscription assessments, and had ever been recorded as being in an opposite-sex marriage or a legally recognized same-sex partnership were included (n = 156,612). Hospital-diagnosed CVD between ages 31 and 58 years was identified using medical records. Men were grouped into an opposite-sex marriage category or a same-sex partnership category based on marital status. Risk factors for CVD in late adolescence were identified using five biomarkers (systolic and diastolic blood pressure, pulse pressure, body mass index, and erythrocyte sedimentation rate) obtained at a conscription examination between ages 16 and 20 years. Birth year, childhood socioeconomic characteristics, physical and psychological characteristics in late adolescence, and mental health before the onset of CVD were treated as potential confounders. Results: Being in a same-sex partnership was associated with increased CVD risk compared with being in an opposite-sex marriage after controlling for potential confounders and risk factors; hazard ratio = 1.61, 95% confidence interval (CI) = 1.27-2.04. The risk factors in late adolescence explained 6.36% (95% CI = 2.72-12.74) of the increased CVD risk associated with being in same-sex partnerships compared with being in opposite-sex marriages. Conclusions: CVD risk factors accumulated by late adolescence may only partially account for the association between same-sex partnerships and cardiovascular health.