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Introduction: Chronic venous disease is a global public health problem, with high morbidity and economic distress. There is scarcity of data on this disease in sub-Saharan Africa. Methods: We conducted the first population-based study over a period of 20 months from 1st February 2020 to 30th September 2021 in the 10 regions of Cameroon. A stratify sampling method was chose to select study site. Socio-demographic data, personal and family history, anthropometric parameters, clinical signs, illustrative images, CEAP (Clinical-Etiological-Anatomical-Pathophysiological) classification revised in 2004, VCSS (venous Clinical Severity Score) and risk factor assessment score were used to construct the survey form. Chi-squared test and Fischer exact test were used to compare the prevalence of chronic venous disease across different potential risk factors (sex, age category, previous history of deep vein thrombosis, hypertension, diabetes, smoking status, obesity). Simple and multiple logistic regression models were used to obtain crude and adjusted odds ratio for risk factors associated with chronic venous insufficiency. Statistical analyses were done with R version 4.2 for Linux and the threshold for statistical significance was 0.05. Results: A total of 6578 participants were included in the study, with a mean age of 41.09 ± 16.02 years with female predominance (54.3%). The prevalence of chronic venous disease was 21.8% (95% CI: 20.8–22.9) and the prevalence of chronic venous insufficiency (C3–C6) was 7.02% (n = 462). Night cramps (43.2%), oedema (21.7%), lower limbs pain (20.4%) mostly worsens by walking and heavy legs (16.2%) were more common symptoms. The mean total venous clinical severity score was 0.69 ± 1.76 and this score had a significant positive correlation with C classification (p <.001). In the multivariate analysis, the following factors were independently associated with CVD: Male gender (aOR: 1.27; 95%CI: 1.04–1.56; p =.021), retired people (aOR: 46.9; 95% CI: 12.6–174.5; p <.001), hypertension (aOR: 289.5; 95%CI: 169.69–493.1; p <.001), diabetes (aOR: 2.19; 95% CI: 1.21–3.96; p =.009), obesity (aOR: 10.22; 95%CI: 7.67–13.62; p <.001). Smoking appears as a protective factor (aOR: 0.18; 95%CI: 0.10–0.30; p <.001). Conclusion: Chronic venous disease is frequent in Cameroon and main traditional cardiovascular risk factors are associated to this condition. Systematic screening of the CVD in these specific groups could reduce the burden of the disease and its economic impact. [ABSTRACT FROM AUTHOR]