Background <p>The aim was the effects of interscalene block (ISB) on blood pressure, focusing on identifying anatomical and clinical predictors of hypertensive responses. The aim is to improve the safety and effectiveness of ISB, especially in patients at increased risk of adverse hemodynamic events.</p> Methods <p>We conducted a prospective cohort study including patients undergoing ISB. Key measurements included carotid intima-media thickness (CIMT), neck length, anterior scalene muscle thickness, BMI, age, history of diabetes mellitus, and hypertension. Blood pressure was monitored at multiple intervals, and logistic regression was used to identify independent systolic blood pressure elevation predictors.</p> Results <p>A total of 110 patients were included in the study. Reduced anterior scalene muscle thickness (OR = 0.620, 95% CI = 0.462–0.833; <i>p</i> = 0.002), increased CIMT (OR = 1.006, 95% CI = 1.002–1.009; <i>p</i> = 0.001), and history of hypertension hypertension (OR = 4.31, 95% CI = 1.173–15.85; <i>p</i> = 0.028), were independent predictors of blood pressure elevation during ISB (<i>p</i> = 0.028, <i>p</i> = 0.001, <i>p</i> = 0.002). CIMT ≥ 750&#xa0;μm and anterior scalene muscle thickness ≤ 12.75&#xa0;mm were identified as critical cut-off values (<i>p</i> &lt; 0.001 for both).</p> Conclusions <p>Preoperative evaluation of anatomical and clinical predictors, such as CIMT and anterior scalene muscle thickness, may improve patient safety, particularly for high-risk individuals during ISB. However, the moderate predictive ability of these factors suggests that they should be considered part of a comprehensive preoperative risk assessment.</p> Trial registration <p>NCT06394960, date: January 25, 2024, first patient registration date: May 2, 2024.</p>