Artifacts caused by regional anesthesia can influence image interpretation of ultrasound and nuclear scintigraphy. Perineural and intrasynovial anesthesia is commonly performed prior to magnetic resonance imaging (MRI); and the effects on MR images, if any, is unknown. The objectives of this prospective, randomized, blinded experiment were to determine if perineural and intrasynovial anesthesia of structures in the equine foot cause iatrogenic changes detectable with MRI. A baseline MRI of both front feet was performed on 15 horses 2 to 6 days prior to mepivacaine injection adjacent to the lateral and medial palmar digital nerves (PDN), and into the podotrochlear bursa (PB), digital flexor tendon sheath (DFTS), and distal interphalangeal joint (DIPJ) of one randomly assigned forelimb. MRI was repeated at 24 and 72 hours post-injection; then qualitative and quantitative assessments of MRI findings were performed. The results of this study showed MRI findings associated with the PDN, PB and DIPJ at 24 and 72 hours after mepivacaine injection did not alter significantly from those at baseline. Compared to baseline, a significant increase in synovial fluid volume of the DFTS was detected with MRI at 24 and 72 hours post-injection. Therefore, perineural anesthesia of the PDN and intrasynovial anesthesia of the PB or DIPJ did not interfere with the interpretation of MRI examinations performed at 24 or 72 hours after injection. However, intrasynovial anesthesia of the DFTS caused an iatrogenic increase in synovial fluid, which was detectable on MRI for at least 72 hours. Although a definite time frame for resolution of DFTS distension was not determined, we recommend waiting greater than 3 days between intrasynovial anesthesia of the DFTS and evaluation with MRI.