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Background: Grip strength is a powerful predictor of disability as well as a good indicator of physical activity. Objectives: This study aimed to relate ultrasound (US) and electromyography (EMG) simultaneously to maximum hand-grip strength during an isometric contraction. Approach: This is a cross-sectional study. Data acquisition was done with a dynamometer, US and EMG. Outcome variables included maximum strength during the hand-grip gesture, maximum muscle activity and change in muscle thickness. A non-linear regression analysis was performed to analyse the relationship between all outcome variables. Main results: A total of 38 subjects (18 men and 20 women) participated in the study. The mean results for hand-grip strength were 25.50 (SD 6.55) kg of maximum strength, a change in muscle thickness of 1.83 (SD 0.75) mm and an EMG activity of 499.29 (SD 224.20) µV. Hand-grip strength had a high correlation with muscle thickness (R2 = 0.61) and EMG activity (R2 = 0.95). The correlation between maximum muscle activity and change in muscle thickness was R2 = 0.83. Significance: The results of the present study demonstrate that this new method based on electromyographic activity and muscule architecture could be important in the development of the hand-grip test.