The analysis of blood alcohol concentration (BAC), a pivotal toxicological test, concerns acute alcohol intoxication (AAI) and driving under the influence (DUI). As such, BAC presents an organizational challenge for clinical laboratories, with unique complexities due to the need for forensic defensibility as part of the diagnostic process. Unfortunately, a significant number of scientific investigations dealing with the subject present discrepancies that make it difficult to identify optimal practices in sample collection, transportation, handling, and preparation. This review provides a systematic analysis of the preanalytical phase of BAC that aims to identify and explain the chemical, physiological, and pharmacological mechanisms underlying controllable operational factors. Nevertheless, it seeks evidence for the necessity to separate preanalytical processes for diagnostic and forensic BAC testing. In this regard, the main finding of this review is that no literature evidence supports the necessity to differentiate preanalytical procedures for AAI and DUI, except for the traceability throughout the chain of custody. In fact, adhering to correct preanalytical procedures provided by official bodies such as European federation of clinical chemistry and laboratory medicine for routine phlebotomy ensures both diagnostic accuracy and forensic defensibility of BAC. This is shown to depend on the capability of modern pre-evacuated sterile collection tubes to control major factors influencing BAC, namely non-enzymatic oxidation and microbial contamination. While certain restrictions become obsolete with such devices, as the use of sodium fluoride (NaF) for specific preservation of forensic BAC, this review reinforces the recommendation to use non-alcoholic disinfectants as a means to achieve “error-proof” procedures in challenging operational environments like the emergency department.