Background: The KEYNOTE-555 trial demonstrated similar efficacy and safety profile of 6-week (q6w) pembrolizumab (400 mg/m²) vs 3-week (q3w) in unresectable and metastatic melanoma leading to FDA’s approval of this dosing schedule for adults in 2020. Limited real-world data is available on the use of 3 weeks vs 6 weeks pembrolizumab in the adjuvant setting in cutaneous melanomas. Q6w is hypothesized to cause more adverse effects due to higher drug concentration. Methods: We conducted a retrospective study of surgically resected Stage IIB-IIID cutaneous melanomas receiving adjuvant pembrolizumab from 2019-2022 at The James Comprehensive Cancer Center with a follow-up of ~1 year. Fifty patients [n=35 (q6w) and n=15 (q3w)] were included. The primary objectives were to compare disease free survival (DFS) and safety profile based on the NCI-CTCAE (v 5.0) criteria. Kaplan-Meier curves were generated for DFS comparisons between the two groups. Fisher’s exact test was used to compare the safety profile between the two groups. Accuracy of the sample size for final analysis was planned based on log rank test. With 15 patients (q3w) and 35 patients (q6w), our study had 80% power to detect differences in clinical outcomes. A p-value of less < 0.05 was considered statistically significant. The secondary objective was to compare overall survival (OS) which will be reported later with a longer follow-up. Results: The mean age in the q6w and q3w groups was 59 years and 69 years, respectively. The median follow up was ~ 9 months with males predominating in both groups (54% and 18%). In the q6w group, 68% had ECOG status 0 (vs.30% in q3w) and most of our patients (32%) were stage IIIB (vs. 6% in q3w) and 28% were stage IIIC (vs 12% in q3wk). BRAF mutation was present in 32% in q6w vs. 2% in q3w. Toxicity profile was noted to be similar in both groups with no significant statistical difference (p-value=0.4), though there were more Grade-3 immune-related toxicities in 7 patients in the q6w group (vs 3 in q3wk). The most common grade 3 toxicity noted was colitis (n=4, q6w; n=1, q3w). Notably, no significant difference was noted in the DFS between the two groups (p-value=0.6). At the time of analysis, 3/15 (20%) patients in q3w and 7/35 (20%) in the q6w group had disease progression with the most common site being the regional lymph-nodes. At the time of the last follow up, 96% of the patients were alive with only 2 deaths occurring due to non-cancer related causes. Conclusions: We demonstrate comparable efficacy of q6w and q3w adjuvant pembrolizumab for advanced stage melanoma, with a trend towards increased immune-mediated colitis events in q6w.