The objective of this systematic review was to determine the effectiveness and safety of propranolol compared to placebo or usual care for improving clinical relevant outcomes in severely burned patients (TBSA >20%). Relevant articles from randomized controlled trials were identified by a literature search in MEDLINE, EMBASE, and CENTRAL. We included trials involving patients with a severe burn (>20% of total body surface area affected). Trials were eligible if they evaluated propranolol and compared to usual care or placebo. Two investigators independently assessed articles for inclusion and exclusion criteria and selected studies for the final analysis. We conducted a meta-analysis using a random-effects model. We included ten studies in our systematic review. These studies randomized a total of 1236 participants. There were no significant differences between propranolol and placebo with respect to mortality (RD −0.02 [95% CI −0.06 to 0.02]), sepsis (RD −0.03 [95% CI −0.09 to 0.04]), and the overall hospital stay (MD −0.37 [−4.52 to 3.78]). Propranolol-treated adults had a decrease in requirements of blood transfusions (MD −185.64 [95% CI −331.06 to −40.43]) and a decreased heart rate (MD −26.85 [95% CI −39.95 to −13.75]). Our analysis indicates that there were no differences in mortality or sepsis in severely burned patients treated with propranolol compared with those who had usual care or placebo. However, the use of propranolol in these patients resulted in lower requirements of blood transfusion and lower values of heart rate. The evidence synthesized in this systematic review is limited to conclude that propranolol reduces the length of hospital stay among severely burned patients. Future trials should assess the impact of propranolol on clinically relevant outcomes such as mortality and adverse events.