Objectives The goal of this study was to define the association between low QRS voltage and cardiac tamponade or pericardial effusion and to assess the reversibility of low QRS voltage after therapeutic procedures. Background It is unclear whether low QRS voltage is a sign of cardiac tamponade or whether it is a sign of pericardial effusion per se. Methods In a prospective study design, we recorded consecutive 12-lead electrocardiograms and echocardiograms in 43 patients who were referred to our institution for evaluation and therapy of a significant pericardial effusion. Cardiac tamponade was present in 23 patients (53%). Low QRS voltage (defined as maximum QRS amplitude <0.5 mV in the limb leads) was found in 14 of these 23 subjects (61%). Nine of these 14 patients were treated by pericardiocentesis (group A). Five patients received anti-inflammatory medication (group B). Group C consisted of nine patients with pericarditis and significant pericardial effusion who had no clinical evidence of tamponade. Results In group A, low QRS voltage remained largely unchanged immediately after successful pericardiocentesis (0.36 <plus/minus> 0.17 mV before vs. 0.42 +/- 0.21 mV after, p = NS), but QRS amplitude recovered within a week (0.78 +/- 0.33 mV, p <0.001). In group B, the maximum QRS amplitude increased from 0.40 <plus/minus> 0.20 mV to 0.80 +/- 0.36 mV (p < 0.001) within six days. In group C, all patients had a normal QRS amplitude initially (1.09 <plus/minus> 0.55 mV) and during a seven-day follow-up (1.10 +/- 0.56 mV, p = NS). Conclusions Low QR voltage is a feature of cardiac tamponade but nt of pericardial effusion per se. Our findings indicate that the presence and severity of cardiac tamponade, in addition to inflammatory mechanisms, may contribute to the development of low QR voltage in patients with large pericardial effusions. (J Col Cardiol 2001;38:219-26) (C) 2001 by the American College of Cardiology.