Background: Many surgeons report pain as a result of muscle fatigue during laparoscopy. Therefore, determining how surgical task or instrument selection influences the duration of muscle activation may provide insight into the relationship between laparoscopic instrumentation and muscle fatigue. Methods: Surface electromyography (EMG) electrodes were placed over the right deltoid, trapezius, bicep, pronator teres, flexor carpi ulnaris, and extensor digitorum superficialis muscles of four surgeons. These surgeons were then asked to perform a targeted grasp and release (T1), a simulated bowel inspection (T2), and a cable-tying exercise (T3) while using three different inline finger-looped graspers. The graspers included a nonratcheted handle with a single-action blunt-end effector (G1) and two models that had ratcheted handles with dual-action end effectors (G2, G3). Resting and maximal voluntary contraction EMG values for each muscle were used to normalize the data and to determine percentage of activation during each task. A multivariate analysis of variance (ANOVA) was used to compare EMG relative time of activation (RAT) patterns with grasper, task, and grasper and task interaction. Results: In general, when grasper and task were considered individually, G1 and T3 demonstrated the highest RAT. Findings showed that RAT was most affected by the use of either G1 or G2 during T2 or T3. Conclusion: Task, grasper, and the interaction between grasper and task all appear to influence the RAT and therefore, to varying degrees, all three may play a role in influencing muscle fatigue.