Measuring electrodermal activity (EDA) on the wrist with the use of dry electrodes is a promising method to help identify person-specific stressors during prolonged recordings in daily life. While the feasibility of this method has been demonstrated, detailed testing of validity of such ambulatory EDA is scarce. In a controlled laboratory study, we examine SCL and ns.SCR derived from wrist-based dry electrodes (Philips DTI) and palm-based wet electrodes (VU-AMS) in 112 healthy adults (57% females, mean age = 22.3, SD = 3.4) across 26 different conditions involving mental stressors or physical activities. Changes in these EDA measures were compared to changes in the Pre-ejection period (PEP) and stressor-induced changes in affect. Absolute SCL and ns.SCR frequency were lower at the wrist compared to the palm. Wrist-based ns.SCR and palm-based ns.SCR and SCL responded directionally consistent with our experimental manipulation of sympathetic nervous system (SNS) activity. Average within-subject correlations between palm-based and wrist-based EDA were significant but modest (r SCL = 0.31; r ns.SCR = 0.42). Changes in ns.SCR frequency at the palm (r = −0.44) and the wrist (r = −0.36) were correlated with changes in PEP. Both palm-based and wrist based EDA predicted changes in affect (6.5%–14.5%). Our data suggest that wrist-based ns.SCR frequency is a useful addition to the psychophysiologist’s toolkit, at least for epidemiology-sized ambulatory studies of changes in sympathetic activity during daily life.