Enrolling severely burn injured patients into prospective research studies poses specific challenges to investigators. The authors describe their experience of recruiting adults with ≥20% TBSA burns or inhalation injury admitted to a single academic burn unit into observational research with minimally invasive specimen collection. The authors outline iterative changes that they made to their recruitment processes in response to perceived weaknesses leading to delays in enrollment. The primary outcome was the change in days to consent for enrolled patients or cessation of recruitment for nonenrolled patients before and after the interventional modifications. The authors assessed change in overall enrollment as a secondary outcome. Study enrollment was approximately 70% in both 4-month study periods before and after the intervention. Following the intervention, time to consent by surrogate decision maker decreased from a median of 26.5 days (interquartile range [IQR] 14–41) to 3 days (IQR 3–6) (P = .004). Time to initial consent by patient changed from a median of 15 days (IQR 2–30) to 3 days (IQR 2–6) (P = .27). Time to decline for nonenrolled patients decreased from a median of 12 days (IQR 6.5–27) to 1.5 days (IQR 1–3.5) (P = .026). Both the findings of the study and a brief literature review suggest that careful design of the recruitment protocol, increased experience of the study team, and broad time windows for both approach and enrollment improve the efficiency of recruiting critically injured burn patients into research.