Background: We aimed to describe the demographic, injury-related, and treatment-related characteristics of patients who undergo fasciotomies for acute hand compartment syndrome. Methods: A cohort of 53 adult patients with acute hand compartment syndrome treated with fasciotomy at 2 tertiary care referral centers over a 10-year time period from January 1, 2006, to June 30, 2015, were retrospectively identified. We reviewed the electronic medical record for patient-related variables (eg, age, sex, smoking status, diabetes mellitus), injury-related variables (eg, mechanism of injury, presence of fractures), and treatment-related variables (eg, compartments released, number of operations, use of split-thickness skin grafts, and time from injury to surgery). Results: The mean age of our cohort was 45 years, and 33 patients (62%) were men. The mechanism of injury varied widely, but the most common causative mechanisms were crush injury (25%), prolonged decubitus (17%), and infection (11%). Associated hand fractures were present in 15 (28%) patients. The surgically released compartments varied; the dorsal interosseous compartments (83%), thenar compartment (75%), and hypothenar compartment (74%) were most frequently released, while the adductor pollicis compartment (43%) and Guyon canal (28%) were least frequently released. Conclusions: The demographics of acute hand compartment syndrome have evolved in the last 25 years compared with the prior literature, partly as a result of the opioid epidemic leading to a rise in “found down” compartment syndrome. Treating providers should recognize crush injury, prolonged decubitus, and infection as the most common causes of acute hand compartment syndrome.