Purpose: The Emergency Department (ED) is an important venue for the care of patients with cancer. We sought to describe the national characteristics of ED visits by patients with cancer in the United States. Methods: We performed an analysis of 2012–2014 ED visit data from the National Hospital Ambulatory Medical Care Survey (NHAMCS). We included adult (age ≥ 18 years) ED patients, stratified by history of cancer. Using the NHAMCS survey design and weighting variables, we estimated the annual number of adult ED visits by patients with cancer. We compared demographics, clinical characteristics, ED resource utilization, and disposition of cancer vs. non-cancer patients. Results: There were an estimated 104,836,398 annual ED visits. Patients with cancer accounted for an estimated 3,879,665 (95% CI: 3,416,435–4,342,895) annual ED visits. Compared with other ED patients, those with cancer were older (mean 64.8 vs. 45.4 years), more likely to arrive by Emergency Medical Services (28.0 vs. 16.9%), and experienced longer lengths of ED stay (mean 4.9 vs. 3.8 h). Over 65% of ED patients with cancer underwent radiologic imaging. Patients with cancer almost twice as likely to undergo CT scanning; four times more likely to present with sepsis; twice as likely to present with thrombosis, and three times more likely to be admitted to the hospital than non-cancer patients. Conclusions: Patients with cancer comprise nearly 4 million ED visits annually. The findings highlight the important role of the ED in cancer care and need for addressing acute care conditions in patients with cancer.