The present study investigated the biomechanical and physiological loads when working with pruning shears of varying design. The objective of this study was to find usability issues on conventional pruning shears and integrate ergonomics into the design process to improve users' safety and health as well as performance. Effects of pruning shear design, gender, and hand size on muscle activities, grip force distribution, wrist deviations, and gender-specific operating strategy were studied in six male and six female participants while cutting wooden dowels with pruning shears. Three types of pruning shears were used, one conventional and two modified, either with a rubber grip-padded, or with a thumb grip attached to the upper handle. The results showed that (1) the two redesigned pruning shears minimized pressures on some critical hand regions and improved muscle activities, grip force distribution, and wrist deviations and (2) a large degree of wrist extension, greater use of the extensor digitorum (ED) muscle, and excessive squeezing force were women's operating strategies to overcome their biomechanical disadvantages due to small hand size and less muscle strength during pruning work. Based on this finding, it was concluded that conventional pruning shears have potential design problems related to musculoskeletal disorders (MSDs), and therefore ergonomic interventions should focus more on variations in user anthropometry and physiological responses.