Sampling error is a common problem in muscle biopsies. MRI-guided biopsy allows verification of biopsy site during the procedure, which may reduce sampling error in patients with focal disease. To describe the technique for MRI-guided muscle biopsy and discuss potential applications. Axial MRI images were acquired to determine the target site for muscle biopsy. Needle trajectory was planned on 3D T1 weighted imaging and a MRI-guided biopsy of the vastus lateralis was performed in 13 FSHD patients. An adequate amount of muscle tissue was obtained in all participants, and MRI-guided biopsy succeeded in reaching focal target sites. However, symptomatic hematomas were observed in 2/13 patientsDiscussion:MRI-guided biopsy has a higher complication rate compared to traditional needle biopsy, most likely due to proximity to blood vessels in combination with the vacuum-assisted suction of the MRI-guided technique. We recommend that this technique is reserved for select diagnostic cases and research questions, with careful assessment of vasculature and reduced suction levels.