To compare the distribution of cardiovascular disease (CVD) factors between continental and Mediterranean areas and urban and rural areas of Croatia, as well as to investigate the differences in achieving treatment goals by the general practitioners (GP) in different settings. A multicenter prospective study was performed on 2467 participants of both sexes ≥40 years old, who visited for any reason 59 general practices covering the whole area of Croatia (May-July 2008). The study was a part of the Cardiovascular Risk and Intervention Study in Croatia-family medicine (CRISIC-fm) study. Patients were interviewed using a 140-item questionnaire on socio-demographics and CVD risk factors. We measured body mass index (BMI) and waist circumference and determined biochemical variables including blood pressure, total, high-density lipoprotein-, and low-density lipoprotein-cholesterol, triglycerides, glycemia, and uric acid. Participants from continental rural areas had significantly higher systolic and diastolic blood pressure (P<0.001), obesity (P=0.001), increased waist circumference (P<0.001), and more intense physical activity (P=0.020). Participants from coastal rural areas had higher HDL-cholesterol, participants from continental rural and coastal urban areas had higher LDL-cholesterol, and participants from rural continental had significantly higher BMI and waist circumference. Prevalence of CVD risk factors in Croatian population is high. Greater burden of risk factors in continental region and rural areas may be partly explained by lifestyle differences.