The use of Y-90 radioembolization techniques has become a standard tool for the treatment of liver cancer and metastatic diseases that result in liver lesions. As there are only two approved forms of radioembolization therapy, the procedures for use are also fairly standardized even though exact international and interdepartmental procedures can vary. What has been less published over the years are the nuanced differences in delivery techniques and handling of the two available Y90 radioembolization therapies. This paper seeks to examine various aspects of delivery techniques, product handling, and radiation exposure that differ between the available and approved products. Understanding these differences can assist with providing more efficient treatment, confirmation of accurate therapy, more informed handling of the products, and improved training of physicians and other hospital staff. Two commercially available and approved radioembolization devices were compared to assess nuanced, but key differences between the available products regarding therapy delivery, handling of the products, and radiation exposure to patients and staff. This work is broken into two sections: (1) Therapy Delivery, (2) Radiation Safety. Therapy delivery characteristics were assessed by using an external radiation detector system with detectors placed inside of each delivery system facing the dose vial and on the output catheter lines to the patient. Additional detectors were placed near the liver of the patient and on top of the foot to measure extremities. Data were acquired continuously throughout therapy delivery to collect time activity curves (TACs) for the characterization of each therapy. These data were analyzed to assess if (a) real-time monitoring of radiation could be used to provide an accurate assessment of residual dose before the patient leaves the procedure room, and (b) can dose delivery characteristics be observed that enable improved training and quality control. Calculation of residual dose using the external detector TACs was performed by analyzing initial and final activity peaks to determine measured count rate differences. Radiation safety aspects were assessed by monitoring radiation exposure to staff handling each of the available therapy products. Nuclear medicine technologists and interventional radiology physician body and hand doses were measured for each delivered therapy using standard body and ring dosimeters. The TACs noted above collected for the liver and extremities were used to assess if any off-target or leached Y90 activity could be detected for each therapy. Blood was collected at times before, during, and after treatment and then counted on a gamma counter to assess differences in free Y90 circulating in the blood. Each patient in this study also received a post-treatment whole-body PET/CT at 2-4 h post-infusion to assess for any aggregate free Y90 deposition that may have resulted from circulating free Y90 in the subject following therapy. Calculations of residual dose in the vial following therapy using the real-time detection methods resulted in values that were not statistically different from the values calculated by nuclear medicine following the procedure ( ). Real-time collection of dose delivery data enabled observation of key characteristics related to each delivery method. For SIR-spheres procedures, the cycle of pushing the dose and visualizing with fluoro can easily be seen with each push resulting in a smaller and smaller peak with intermittent fluoroscopy pulses. TheraSpheres infusions show a rapid bolus with nearly all of the measurable injected activity being infused in the first push of the dose. Staff radiation exposure assessments showed statistically significant differences between glass and resin spheres for hand doses of physicians and technologists (p > 0.05), but no statistical difference between body doses for both products ( ). Assessments of free Y90 circulating during therapy showed that patients undergoing therapies with resin spheres had post-infusion blood levels that were 120% higher than pre-infusion levels while glass sphere therapy patients only saw a 7% rise in post-infusion blood levels. The coefficients of variation (COVs) across glass sphere measurements pre, during, and post, were only 0.008 while resin sphere measures saw much greater variability with a COV of 0.45. Both glass and resin therapies showed blood levels at 2-4 h post-injection to be similar to levels measured pre-injection. Neither therapy showed any signs of focal aggregation at 2-4 h post-infusion on whole-body PET/CT. Although glass and resin radioembolization therapies are similar, they both have unique characteristics related to their administration and handling by staff. Understanding the nuances can assist in providing more efficient delivery, better staff education, and reducing radiation exposure to everyone involved with these therapies. The use of near real-time monitoring is feasible and can be used to obtain critical information about the delivery success of a therapy and can inform physicians on their techniques to optimize their practice as well as provide more consistent training to residents.