Sinusoidal obstruction syndrome (SOS) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Traditional ultrasound (US) has poor sensitivity and specificity. US shear wave elastography (SWE) is a newer technology that measures liver stiffness. This is a single-institution, prospective cohort study evaluating SWE in patients younger than 21 years who received HSCT from December 2015 through June 2017. SOS was defined using the modified Seattle criteria. Subjects had US with SWE at three scheduled time points. t-tests were used to assess for difference between the groups and ROC curves were generated. Twenty-five patients were included. Five subjects developed SOS. At day +5 HSCT, SOS patients had SWE velocities that increased by 0.25 ± 0.21 m/s compared to 0.02 ± 0.18 in patients without SOS (p = 0.020). At day +14, SOS patients had SWE velocities that significantly increased by 0.91 m/s ± 1.14 m/s compared to 0.03 m/s ± 0.23 m/s in patients without SOS (p = 0.010). SWE SOS diagnosis occurred on average 9 and 11 days before clinical and conventional US diagnosis, respectively. Patients who develop SOS have increased liver stiffness compared to patients who do not develop SOS. SWE changes occur before other imaging and clinical findings of SOS.