The clinical evaluation of acute mountain sickness (AMS) is often performed in remote settings with minimal equipment. The purpose of this study was to examine the utility of heart rate variability and other cardiovascular parameters in a high-altitude clinical setting. Forty-one participants were recruited from the patient population of the clinic, and from festivalgoers [those who attended the Janai Purnima festival held at Lake Gosainkunda (4380 m) in Langtang, Nepal] in the vicinity of the clinic. Twenty-one participants were diagnosed with AMS; remaining participants were free from altitude illness. Heart rate variability (both time and frequency domain measures), arterial oxygen saturation (SpO2), blood pressure and Lake Louise Score were evaluated in all the participants. Oxygen saturation and diastolic blood pressure were negatively and positively correlated with Lake Louise Score, respectively. Receiver operating characteristic analysis indicated that an SpO2 of 86% or greater was associated with a very low likelihood of AMS at this altitude. No heart rate variability parameters were different in the AMS group as compared with the control group. In conclusion, in patients with SpO2 of 86% or more at 4380 m or higher, the likelihood of AMS is low. Diastolic blood pressure correlated with AMS severity, whereas heart rate variability was not useful in the diagnosis of AMS.