Abstract <p>Video laryngoscopy has become an integral part of today’s airway management. Despite its advantages, loss of depth perception and increased cognitive load remain a challenge and not all airway scenarios can be successfully managed and resolved. This study aims to evaluate the efficacy of larynGuide, an AI-based software integrated with the C-MAC video laryngoscope, in improving tracheal intubation success rates. This prospective, randomized, 2 × 2 crossover, simulation-based study included 74 medical professionals, 35 experienced and 39 inexperienced participants. Each participant performed tracheal intubations using a C-MAC video laryngoscope with and without the larynGuide AI overlay in both easy and difficult airway scenarios. The primary outcome was the first attempt success rate. Secondary outcomes included overall success rate, time to intubation, procedural performance scores, and incidence of dental injury. Data were analyzed using mixed effects models with binomial response and non-parametric tests as appropriate. The overall first attempt success rate was 89% with larynGuide and 85% with standard C-MAC, the odds of successful intubation were 72% higher with larynGuide (OR = 1.72, 95%CI = 1.08, 2.73; p = 0.022). Among experienced participants, the benefit was more pronounced (OR = 3.37, 95%CI = 1.2, 8.9; p = 0.016). Time to intubation was longer with larynGuide (median = 29 s) compared to standard C-MAC (median = 23 s, p &lt; 0.01). The incidence of dental damage was lower with larynGuide (22%) compared to C-MAC (27%), although not statistically significant (p = 0.095). The larynGuide AI-powered software improved tracheal intubation success rates compared to standard C-MAC videolaryngoscopy in this simulation-based study, highlighting the potential role of AI in enhancing airway management. Further clinical studies are needed to confirm these results and support broader integration into practice.</p> Trial registration <p>ClinicalTrials.gov ID NCT06657417.</p>