Objective: To assess the prevalence and clinical implications of variant sciatic nerve anatomy in relation to the piriformis muscle on magnetic resonance neurography (MRN), in patients with lumbosacral neuropathic symptoms. Materials and Methods: In this retrospective single-center study, 254 sciatic nerves, from 127 patients with clinical and imaging findings compatible with extra-spinal sciatica on MRN between 2003 and 2013, were evaluated for the presence and type of variant sciatic nerves, split sciatic nerve, abnormal T2-signal hyperintensity, asymmetric piriformis size and increased nerve caliber, and summarized using descriptive statistics. Two-tailed chi-square tests were performed to compare the anatomical variant type and clinical symptoms between imaging and clinical characteristics. Results: Sixty-four variant sciatic nerves were identified with an equal number of right and left variants. Bilateral variants were noted in 15 cases. Abnormal T2-signal hyperintensity was seen significantly more often in variant compared to conventional anatomy (40/64 vs. 82/190; p = 0.01). A sciatic nerve split was seen significantly more often in variant compared to conventional anatomy (56/64 vs. 20/190; p p p = 0.01). Conclusion: Variant sciatic nerve anatomy, in relation to the piriformis muscle, is frequently identified with MRN and is more likely to be associated with nerve signal changes and symptomatology.