An algorithm for analyzing changes in ECG morphology based on principal component analysis (PCA) is presented and applied to the derivation of surrogate respiratory signals from single-lead ECGs. The respiratory-induced variability of ECG features, P waves, QRS complexes, and T waves are described by the PCA. We assessed which ECG features and which principal components yielded the best surrogate for the respiratory signal. Twenty subjects performed controlled breathing for 180 s at 4, 6, 8, 10, 12, and 14 breaths per minute and normal breathing. ECG and breathing signals were recorded. Respiration was derived from the ECG by three algorithms: the PCA-based algorithm and two established algorithms, based on RR intervals and QRS amplitudes. ECG-derived respiration was compared to the recorded breathing signal by magnitude squared coherence and cross-correlation. The top ranking algorithm for both coherence and correlation was the PCA algorithm applied to QRS complexes. Coherence and correlation were significantly larger for this algorithm than the RR algorithm(p < 0.05 and p < 0.0001, respectively) but were not significantly different from the amplitude algorithm. PCA provides a novel algorithm for analysis of both respiratory and nonrespiratory related beat-to-beat changes in different ECG features.