Patients with advanced- or terminal-stage cancer and persons receiving palliative care are at high risk for pressure ulcers (PUs). Purpose The purpose of this study was to examine the rate of PU development and levels of comfort of a dual-fit, air-cell mattress compared with an alternating, 2-layer overlay air-cell mattress in patients with advanced- or terminal-stage cancer receiving palliative care. Methods From January 2011 to December 2013, hospitalized patients with advanced- or terminal-stage cancer who were referred to a palliative care team, at least 20 years of age, able to communicate, experiencing pain, and did not have a PU were recruited to participate. Patients who consented were alternately placed on the intervention (dual-fit, air-cell) or control (2-layer air) mattress until hospital discharge or death. Demographic and clinical data, pain scores, performance status, Palliative Performance Scale scores, Braden Scale scores, tissue interface pressure, and comfort were assessed via interview using closed-end questions. If a PU developed, clinical characteristics were assessed using DESIGN-R. Descriptive statistics and the Mann-Whitney U, chi-squared, and Fisher's exact tests were used to analyze the data. Results Of the 123 eligible patients, 73 were randomized and 52 completed the study (23 intervention patients, median age 63 [range 27-80] years; and 29 control group patients, median age 61.0 [range 27-82] years). Mattresses were used a median of 17 (range 4-113) days in the intervention group and a median of 32 (range 3-270) days in the control group. The incidence of PUs did not significantly differ between the 2 groups (13% in the intervention and 17.2% in the control group). Interface pressures were significantly higher in the intervention group (27.0 mm Hg vs. 24.3 mm Hg). Comfort scores at rest were significantly better in the intervention than in the control group (sinking into bed [3 vs. 14, respectively]; slipping on bed [o vs. 16, respectively]; and feel pressure of air cell [2 vs. 14, respectively]), as were scores with movement (instability during movement [4 vs. 18, respectively] and feeling of floating of the buttocks [6 vs. 21, respectively]) (P Conclusion Dual-fit, air-cell mattresses may help prevent PUs and improve comfort at rest and during activity among patients with end-stage cancer receiving palliative care. Further research regarding mattress selection protocols for this patient population is warranted.