Abstract Background Originally, the cranks of a handcycle were mounted with a 180° phase shift (asynchronous). However, as handcycling became more popular, the crank mode switched to a parallel mounting (synchronous) over the years. Differences between both modes have been investigated, however, not into great detail for propulsion technique or practice effects. Our aim is to compare both crank modes from a biomechanical and physiological perspective, hence considering force and power production as a cause of physiological outcome measures. This is done within a practice protocol, as it is expected that motor learning takes place in the early stages of handcycling in novices. Methods Twelve able-bodied male novices volunteered to take part. The experiment consisted of a pre-test, three practice sessions and a post-test, which was subsequently repeated for both crank modes in a counterbalanced manner. In each session the participants handcycled for 3 × 4 minutes on a leveled motorized treadmill at 1.94 m/s. Inbetween sessions were 2 days of rest. 3D forces, handlebar and crank angle were measured on the left hand side. Kinematic markers were placed on the handcycle to monitor the movement on the treadmill. Lastly, breath-by-breath spirometry combined with heart-rate were continuously measured. The effects of crank mode and practice-based learning were analyzed using a two way repeated measures ANOVA, with synchronous vs asynchronous and pre-test vs post-test as within-subject factors. Results In the pre-test, asynchronous handcycling was less efficient than synchronous handcycling in terms of physiological strain, force production and timing. At the post-test, the metabolic costs were comparable for both modes. The force production was, also after practice, more efficient in the synchronous mode. External power production, crank rotation velocity and the distance travelled back and forwards on the treadmill suggest that asynchronous handcycling is more constant throughout the cycle. Conclusions As the metabolic costs were reduced in the asynchronous mode, we would advise to include a practice period, when comparing both modes in scientific experiments. For handcycle users, we would currently advise a synchronous set-up for daily use, as the force production is more effective in the synchronous mode, even after practice.