The objective of this study was to examine the clinical and genetic variables associated with extra-articular rheumatoid arthritis (ExRA). This was a cross-sectional study in which 538 Northwestern Colombian patients with rheumatoid arthritis (RA) were included. Information about demographics and clinical characteristics including disease activity, inflammatory markers, co-morbidities, cardiovascular (CV) risk factors, history of familial autoimmunity and therapy was recorded. The presence of HLA "shared epitope" (SE) alleles and TNF gene polymorphism was assessed. A multivariate statistical analysis was performed. ExRA was found in 32% of the patients, of which nodulosis, Sjögren's syndrome, and lung involvement were registered in 21%, 9%, and 4% of patients, respectively. Patients with ExRA were older than patients without it and they presented longer disease duration as well. Thus, an association between disease duration and ExRA manifestations was also observed. Patients with ExRA presented significant higher titers of anti-CCP antibodies as compared to patients without ExRA. Hypertension and thrombosis were significantly associated with ExRA. Never having smoked constituted a protective factor against ExRA onset. Associations between ExRA and the presence of traditional CV risk factors were also found. Our results show that duration of RA, CV disease and high titers of anti-CCP antibodies are associated with ExRA in Colombian patients with RA, and highlight the importance of preventing smoking in those who are prone to develop autoimmune diseases including RA.