This prospective, observational, multicenter study assessed the tolerance of Dobenox Forte®, the first approved over-the-counter product containing calcium dobesilate, in 1795 outpatients with chronic venous disease (CVD) in daily clinical practice. In addition, the effectiveness (decrease in circumferences of a more affected limb at the ankle and middle part of the calf, and changes in the severity of CVD signs) was assessed. No adverse events related to use of the preparation were reported in a period of 64 ± 20 days. Dobenox Forte® use was associated with a reduction in calf circumference by 13.1 mm (95%CI: 12.2-14.1) and in ankle circumference by 9.7 mm (95%CI: 9.2-11.0) in patients reporting swelling of the lower legs (60.0% of the cohort). A reduction in calf and ankle circumference by at least 1 cm was achieved in 34.9% and 24.9% of patients, respectively. The percentages of patients reporting moderate to very severe lower limb heaviness decreased from 96.6% to 56.0%, calf cramps decreased from 91.0% to 41.0%, calf pain decreased from 89.2% to 43.7%, swelling decreased from 86.1% to 38.8%, and burning sensation that worsens when standing decreased from 79.0% to 33.7%. The medicinal product Dobenox Forte® is well tolerated by patients and seems to effectively reduce the symptoms of CVD.