BACKGROUND: The current study explores the trends in the application of combat casualty care following the publication of clinical practice guidelines (CPGs) in five domains for 13 years. METHODS: The Israel Defense Forces Trauma Registry was used to assess practice and adherence to guidelines in five domains: (a) crystalloid transfusions, (b) tranexamic acid use, (c) freeze-dried plasma use, (d) chest decompression, and (e) airway management. All patients injured between January 2006 and December 2018 were included in the analysis. Trends were analyzed and presented monthly using linear regression and were compared using the Chow test. RESULTS: The mean ± SD crystalloid volume transfused decreased from 1,179 ± 653 mL in 2006 to 466 ± 202 mL in 2018 (B = 0.016, 0.006-0.044). The proportion of patients with an indication treated with tranexamic acid dropped from 8% (238 of 2,979 patients) to 2.5% (60 of 2,356 patients) following the stricter guideline's publication. Freeze-dried plasma administration in indicated casualties rose from 12.5% in 2013 to 48% in 2018 (B = 1.63, 1.3-2.05). The overall proportion of casualties undergoing chest decompression rose from 1% (61 of 6,036 casualties) to 1.5% (155 of 10,493 casualties) following the release of a new CPG in 2012 (p = 0.013). There were no significant trends in intubation ratios before (B = 0.987, 0.953-1.02) or after 2012 (B = 10.2, 0.996-1.05). CONCLUSION: Some aspects demonstrate the desired trends in response to new CPGs; in others, initial improvement is achieved but followed by stagnation. In some medical care aspects, completely unexpected and undesirable trends are observed. Every change and update in CPGs should be based on reliable data. The effect of every change must be monitored carefully to ensure adequate adherence to lifesaving guidelines. LEVEL OF EVIDENCE: Epidemiological study, level IV.