The drag force coefficients of a flexible riser undergoing vortex-induced vibration (VIV) in sheared flow are investigated for Reynolds numbers (Re) up to 1.2×105. Based on the drag forces theoretically calculated by the beam theory using the strains measured in a scale model test, the properties and distribution of the drag coefficients are investigated, and a new empirical model for estimating the drag coefficient on a flexible riser undergoing VIV is proposed. The results show that VIV leads to non-uniform distribution of the drag coefficient and amplifies the drag coefficient, and the local drag coefficient can reach up to 3.2. For Re values from 1.0×104–1.2×105, the mean drag coefficient is between 1.3 and 2.0 and decreases as Re increases. Furthermore, the empirical drag coefficient prediction model obtained from experiments under low Re is not suitable for high Re. The corrected empirical prediction model, which accounts for the effect of the flow velocity, the VIV dominant mode number and the dominant frequency, can be used to predict riser drag coefficients under VIV more accurately at high Re values up to 1.2×105. •Drag coefficients for flexible risers under VIV were experimentally investigated.•VIV amplifies drag coefficients. Local drag coefficient of risers can reach 3.2.•Drag coefficient is between 1.3 and 2.0, and decreases as Re increases.•An empirical prediction model is proposed for estimating the drag coefficient.