Running brings many health benefits, but can lead to injuries to the musculoskeletal system. Modern running shoes have been developed to improve running biomechanics, including the heel-to-toe-drop (HTD) which has been highlighted as a central feature in shoe design. The purpose of this study was to investigate impact force characteristics, joint kinematics and kinetics across three commonly-available HTDs, as well as between running with HTDs and barefoot. Fifteen recreational runners took part in this study. Full-body kinematics and ground reaction force (GRF) data were collected while the participants ran at a speed of 4 m/s in three different shoe conditions (4 mm, 8 mm, and 12 mm HTD) as well as barefoot. Comparisons between the four conditions were made for GRFs, joint kinematics and kinetics of the lower extremities. The results primarily showed that a 4 mm HTD led to increased vertical loading rate and maximum ankle moment and a decreased maximum knee moment compared to 8 mm and 12 mm HTD. In addition, differences in ankle and knee kinematics were seen between running in shoes and running barefoot. A lower HTD mainly altered the kinetics of the ankle and knee. Running with a low HTD did not lead to similar lower limb biomechanics as barefoot running. These findings are important because a deeper understanding of biomechanical responses may lead to more customized footwear, which could decrease the risk of running-related injuries.