This study evaluated the effect of hand anthropometry and screen curvatures of handheld devices on hand comfort during single‐hand touchscreen operations. By employing both subjective ratings and electromyography methods, the comfort level was measured using three mock‐up devices with different curvatures; one was flat and the others had curvatures of 400 R and 100 R. The participants were classified by sizes and shapes of their preferred hand based on factor analysis results. In this study, 26 adults in their 20s and 30s participated in the experiment of tapping and dragging tasks with the mock‐ups. The results indicated that the curvatures of the handheld touchscreen devices did not affect muscle activity but perceived comfort. On the other way around, size and shape of hand were found as the factors to affect muscle activities but not perceived comfort. The interaction effects between size and shape of hand were found as well. Overall, this study suggests that curvature and anthropometric characteristics of hand is the common factor in determining comfort for the handheld device design. © 2016 Wiley Periodicals, Inc.