Alterations in dehydroepiandrosterone sulfate (DHEAS) levels have been shown to affect the cardiovascular system. This study examined the associations between DHEAS levels and cardiovascular risk in workers of a public hospital in Lima, Peru. The analytical cross-sectional study was conducted at the Hospital de Huaycán, Peru. The cardiovascular risk was assessed in health workers using the Framingham score and categorized into high and low cardiovascular risk groups, and then the DHEAS levels of both groups were compared. Two hundred ninety-six health workers were studied, 67.2% showed low cardiovascular risk, 22.3% intermediate and 10.5% high. DHEAS levels were lower in the high cardiovascular risk group (2156.9 vs 2814.6 ng/mL; P < 0.05) and showed negative association (prevalence rate ratio 0.14, 95% IC 0.04–0.53; P < 0.05) in multivariable analysis (P < 0.05). DHEAS, glycosylated hemoglobin, pulse pressure and mean arterial pressure show an independent association with high cardiovascular risk in a group of health workers. Additional variables should be considered for cardiovascular risk assessment.