Abstract Background This study aimed to evaluate the accuracy of ankle blood pressure measurements in relation to invasive blood pressure in the lateral position. Methods This prospective observational study included adult patients scheduled for elective non-cardiac surgery under general anesthesia in the lateral position. Paired radial artery invasive and ankle noninvasive blood pressure readings were recorded in the lateral position using GE Carescape B650 monitor. The primary outcome was the ability of ankle mean arterial pressure (MAP) to detect hypotension (MAP < 70 mmHg) using area under the receiver operating characteristic curve (AUC) analysis. The secondary outcomes were the ability of ankle systolic blood pressure (SBP) to detect hypertension (SBP > 140 mmHg) as well as bias (invasive measurement – noninvasive measurement), and agreement between the two methods using the Bland-Altman analysis. Results We analyzed 415 paired readings from 30 patients. The AUC (95% confidence interval CI) of ankle MAP for detecting hypotension was 0.88 (0.83–0.93). An ankle MAP of ≤ 86 mmHg had negative and positive predictive values (95% CI) of 99 (97–100)% and 21 (15–29)%, respectively, for detecting hypotension. The AUC (95% CI) of ankle SBP to detect hypertension was 0.83 (0.79–0.86) with negative and positive predictive values (95% CI) of 95 (92–97)% and 36 (26–46)%, respectively, at a cutoff value of > 144 mmHg. The mean bias between the two methods was − 12 ± 17, 3 ± 12, and − 1 ± 11 mmHg for the SBP, diastolic blood pressure, and MAP, respectively. Conclusion In patients under general anesthesia in the lateral position, ankle blood pressure measurements are not interchangeable with the corresponding invasive measurements. However, an ankle MAP > 86 mmHg can exclude hypotension with 99% accuracy, and an ankle SBP < 144 mmHg can exclude hypertension with 95% accuracy.