Introduction: Recently, ultrasound (US) imaging has been used to estimate the cross-sectional area of skeletal muscle, but the reliability is uncertain. To improve the reliability of the US, we investigated skeletal muscle thickness measurement using an inertial measurement unit (IMU) to determine the direction of US beam incidence based on posture angle information. In addition, we examined whether the anatomical cross-sectional area (ACSA) of muscle can be estimated from the muscle thickness measured using the US with the IMU. Methods: In Experiment 1, two examiners measured the right psoas major at the fourth lumbar vertebra level in 10 university students using the US with and without an IMU. The intraclass correlation coefficient (ICC) was used to examine intra- and inter-rater variability. In Experiment 2, the two examiners measured the muscle thickness of the right psoas major in 31 male subjects using the US with an IMU. In addition, the ACSA of this muscle was measured using MRI. Pearson's correlation coefficient was used to examine the relationship between muscle thickness and ACSA, and a single regression analysis was performed. Results: Both intrarater reliability ICC (1, 2) and inter-rater reliability ICC (2, 2) were higher when US was used with IMU compared to without IMU (Experiment 1). A significant positive correlation (r = 0.84, p < 0.01) was observed between muscle thickness and ACSA (Experiment 2). The regression equation was significant at R 2 = 0.71 (p < 0.01). Conclusion: Using an IMU during US measurement of the psoas major improves intra- and interexaminer reliability and can be used to estimate the ACSA of the muscle.