Pain is one of the major stressors for critically ill patients. The first step for effective pain management is pain assessment. Due to the availability of physiologic monitoring devices in intensive care units, observing changes in vital signs provides a fast, simple, and objective method. However, the validity of physiologic indicators in pain assessment is still debatable. The aim of this study was to validate the discriminant and criterion validity of physiologic indicators for pain assessment in nonverbal patients. The study included 120 patients from the intensive care unit of a medical center of Taiwan. Patients were observed under two nursing procedures to examine the discriminant validity of physiologic indicators: 1) a nociceptive procedure: suctioning; 2) a non-nociceptive procedure: taking noninvasive blood pressure. Forty-four consciously ventilated patients were also asked to provide self-reported pain intensity. Discriminant validity was supported with higher heart rate and blood pressure during suctioning than the values before and after suctioning. Moreover, the heart rate and blood pressure during suctioning were significantly higher than the values during noninvasive blood pressure measurement. In terms of criterion-related validity, there was no significant correlation between patient's self-report of pain intensity and heart rate and blood pressure. As recommended by other scholars and researchers, heart rate and blood pressure can only be used as a cue for pain assessment. If pain is suspected, further appropriate assessment is necessary to provide accurate judgment.