Background: Prior clinical trials in melanoma have demonstrated higher rates of irAEs from combination ICI therapy compared to monotherapy. However, this has not been well studied in the real-world where patients often have greater co-morbidities and less organ reserve. We aim to compare irAEs hospitalizations for melanoma patients on combination vs monotherapy ICIs. Methods: We performed a single centre retrospective chart review (Princess Margaret Cancer Centre, Toronto, ON) for all melanoma patients receiving ICI as standard of care (2012-2017) admitted with irAEs. Data collected include demographics, investigations, management and outcomes of hospitalizations. Descriptive analyses were performed to characterize hospitalizations and compare between ICI combination vs monotherapy groups. Results: Among 381 melanoma patients identified on standard of care ICI, 41 (11%) were admitted for irAE. Among those admitted, 10% received monotherapy with nivolumab, 22% pembrolizumab, 39% ipilimumab and 29% combination ICI. Admission rates were higher among patients receiving combination ICI compared to monotherapy (20% vs 8% p = 0.003). Prevalence of the most common irAEs were similar between combination and monotherapy groups: colitis (58% vs 59%), pneumonitis (8% vs 14%) and hepatitis (8% vs 10%). Less than half received invasive diagnostic tests (i.e, endoscopy) (42% combination vs 35% monotherapy, p = 0.50) with 3 (60%) and 5 (50%) confirming irAEs, respectively. Rates of infliximab use were similar between the combination and monotherapy group (25% vs 21%, p = 0.70). Average length of stay was shorter for patients on combination ICI compared to monotherapy (5 days vs 15 days, p = 0.08). irAE readmission rates were similar between patients receiving combination ICI compared to monotherapy (20% vs 17%, p = 0.65). Conclusions: Despite higher admission rates among patients receiving combination ICI, there was a trend towards shorter hospitalizations. Other outcomes including diagnoses, investigations and management were not significantly different between patients receiving combination vs ICI monotherapy.