Background As part of preoperative patient evaluations, it is customary to estimate the likelihood of difficulties during laryngoscopy and intubation. A diverse array of predictors is frequently employed by anesthesiologists to anticipate difficult laryngoscopy (DL); however, no single predictor has been established as the gold standard. In the present study, we compared routine preoperative ultrasound-guided airway examination and clinical airway examination in predicting DL in patients coming for elective surgery. Methodology The present study is a single-blinded observational study that spanned 12 months, beginning in March 2018 and concluding in February 2019. The study took place at Kovai Medical Center and Hospital (KMCH), which is a tertiary-care facility in Coimbatore, India. The data were obtained through face-to-face interviews, with a sample size of 135 research participants. The questionnaire contained comprehensive data regarding the patient's age, weight, gender, comorbidities, planned surgery, and preoperative assessment, which encompassed a detailed examination of the airway. The clinical airway examination comprised assessing mouth opening, performing the modified Mallampati test, measuring thyromental height (TMH) and thyromental distance (TMD), evaluating neck circumference, and observing neck extension. Ultrasound-guided airway examination was performed during the immediate pre-operative period, focusing on specific parameters such as the pre-epiglottic space, anterior neck soft tissue at the level of vocal cords, thyrohyoid membrane, suprasternal notch, hyoid bone (single parameter measured at different levels), hyo-mental ratio, and tongue volume (TV). Results Among the ultrasound parameters, TV (72.15 cm 3 ) is the best ultrasound parameter to predict DL (95% CI: 0.65 to 0.82), with a high sensitivity of 82% and specificity of 45.88%. Other parameters that are useful are anterior neck soft tissue at the level of the thyrohyoid membrane (0.67 cm), suprasternal notch (1.01 cm), and, lastly, pre-epiglottic space (0.57 cm). Among clinical parameters, modified Mallampati grade (grade 3 or more) is the best parameter to assess the airway clinically and predict DL, followed by neck circumference (>42 cm) and TMH (>5 cm). Based on the findings, we observed that both clinical and ultrasound parameters are comparable to predict DL. Conclusion We observed that routine clinical airway examination and ultrasound examination yielded comparable results in predicting DL. Therefore, the routine use of clinical airway examination still holds good in predicting DL., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of KMCH Limited, Coimbatore issued approval EC/AP/566/10/2017. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Andrews et al.)