Left ventricular hypertrophy is 1 of the most frequent cardiac manifestations associated with an unfavorable prognosis. However, many different causes of left ventricular hypertrophy exist. The aim of the present study was to assess the diagnostic value of common electrocardiographic (ECG) parameters to differentiate Fabry disease (FD), amyloidosis, and nonobstructive hypertrophic cardiomyopathy (HC) from hypertensive heart disease (HHD) and aortic stenosis (AS). In 94 patients with newly diagnosed FD (n = 17), HHD (n = 20), amyloidosis (n = 17), AS (n = 20), and HC (n = 20), common ECG parameters were analyzed and tested for their diagnostic value. A stepwise approach including the Sokolow-Lyon index, corrected QT duration, and PQ interval minus P-wave duration in lead II to overcome P-wave abnormalities was applied. A corrected QT duration <440 ms in combination with a PQ interval minus P-wave duration in lead II <40 ms was 100% sensitive and 99% specific for the diagnosis of FD, whereas a corrected QT duration >440 ms and a Sokolow-Lyon index ≤1.5 mV were found to have a sensitivity and specificity of 85% and 100%, respectively, for the diagnosis of amyloidosis and differentiation from HC, AS, and HHD. Moreover, a novel index ([PQ interval minus P-wave duration in lead II multiplied by corrected QT duration]/Sokolow-Lyon index) proved to be highly diagnostic for the differentiation of amyloidosis (area under the curve 0.92) and FD (area under the curve 0.91) by receiver operator characteristic analysis. In conclusion, a combined analysis of PQ interval minus P-wave duration in lead II, corrected QT duration, and Sokolow-Lyon index proved highly sensitive and specific in the differentiation of FD, amyloidosis, and HC compared to HHD and AS. Analysis of these easy-to-assess ECG parameters may be of substantial help in the diagnostic workup of these 5 conditions.