Background: Recently approved immune checkpoint inhibitors targeting CTLA-4 (ipilimumab) and PD-1 (nivolumab and pembrolizumab) have gained a tremendous amount of attention for their efficacy, but also for their high cost and incidence of side effects. Most discussions of cost have focused on the price of the drugs themselves; however, this model estimates the total cost of treatment including the cost of managing toxicities. Methods: Drug costs were calculated utilizing Redbook average wholesale cost per dose and the average number of doses received by patients at H. Lee Moffitt Cancer Center (N=627). Major toxicities associated with each drug were identified from package inserts and peer-reviewed literature. Toxicity costs were obtained from peer-reviewed literature. Incidences of toxicities were obtained from patient data available in the Total Cancer Care database. The weighted average cost of managing toxicities associated with each drug was calculated and compared to the total anticipated cost of therapy. All cost estimates are in 2015 USD. Results: All three drugs have a similar estimated cost of managing toxicities with nivolumab estimated to be most costly (Table). Ipilimumab is estimated to cost the most per patient driven by the cost of drug. However, toxicities make up a much larger proportion of the cost of care for the PD-1 inhibitors. Conclusions: The cost of managing toxicities associated with immune checkpoint inhibitor therapy is not insignificant and could change the value-to-cost ratio between equally effective drugs, e.g. nivolumab and pembrolizumab.