Introduction: Endoscopic submucosal dissection (ESD) is a novel, minimally invasive method for the removal of malignant and premalignant gastrointestinal lesions. Literature has been published establishing the safety and efficacy of ESD and its potential as a replacement for invasive surgery in some patients. Due to a lack of procedure-specific Current Procedural Terminology (CPT) codes many hospitals are challenged with adopting this intricate procedure in a cost-effective manner. The aim of this study was to evaluate the financial metrics from our first three years of ESD practice and gain insight into how to provide this service more cost-effectively. Methods: Financial data was reviewed from ESDs performed at our tertiary care center from 4/2018 to 3/2021 including insurance status, direct costs, charges per case, payments per case, and contribution margin. Pearson’s correlation test was utilized to assess whether charges, payments, and margins correlated within the cohort. Results: A total of 57 procedures were included, of which 7 were performed inpatient (12.2%) and 50 were outpatient (87.8%). Eleven [19.3%] had commercial insurance, 4 [7.0%] had Medicaid, 34 [59.6%] had Medicare, 4 [7.0%] had federal assistance, and 4 [7.0%] utilized a local repayment assistance program. Total charges [median, range] were $1,718,349 [$17,364, $249,687]. Total direct costs were $409,572 [$4,682, $57,446]. Total payments were $217,488 [$1,199, $50,138]. The total contribution margin was -$183,024 [-$3,334, $21,269]. Increasing charges and costs were associated with increased institutional payments while none were associated with contribution margins. Conclusion: The data depicts an overall net loss for nearly all performed ESDs. Notably, only four of the 57 ESDs yielded a positive contribution margin with three of the most recent seven ESDs netting an average of $6,538 per case. This potentially indicates increased financial viability as more experience was gained with both performing and billing ESDs. Standard deviations exceeded the mean in all fields, indicating a significant degree of variability between procedures. Until standardized CPT codes are established, ESD must be undertaken with a cost-conscious and outcomes-focused mindset to reduce institutional losses.Figure 1.: Top: Depicts relation between costs per case in relation to payments showing a strong correlation. Bottom Left: Relation between charges per case and contribution margin (CM). Bottom Right: Relation between payments per case and CM. It is notable that both bottom figures do not have statistically significant correlations. However, if outliers are not considered, there appears to be a clear negative trend in CM with increasing charges and costs per case.