We propose a low-latency approach for generating secure electrocardiogram (ECG) feature-based cryptographic keys. This is done by taking advantage of the uniqueness and randomness properties of ECG’s main features. This approach achieves a low-latency since the key generation relies on four reference-free ECG’s main features that can be acquired in short time. We call the approach several ECG features (SEF)-based cryptographic key generation. SEF consists of: 1) detecting the arrival time of ECG’s fiducial points using Daubechies wavelet transform to compute ECG’s main features accordingly; 2) using a dynamic technique to specify the optimum number of bits that can be extracted from each main ECG feature, comprising of PR, RR, PP, QT, and ST intervals; 3) generating cryptographic keys by exploiting the above-mentioned ECG features; and 4) consolidating and strengthening the SEF approach with cryptographically secure pseudo-random number generators. Fibonacci linear feedback shift register and advanced encryption standard algorithms are implemented as the pseudo-random number generator to enhance the security level of the generated cryptographic keys. Our approach is applied to 239 subjects’ ECG signals comprising of normal sinus rhythm, arrhythmia, atrial fibrillation, and myocardial infraction. The security analyses of the proposed approach are carried out in terms of distinctiveness, test of randomness, temporal variance, and using National Institute of Standards and Technology benchmark. The analyses reveal that the normal ECG rhythms have slightly better randomness compared with the abnormal ones. The analyses also show that the strengthened SEF key generation approach provides a higher security level in comparison to existing approaches that rely only on singleton ECG features. For the normal ECG rhythms, the SEF approach has in average the entropy of about 0.98 while cryptographic keys which are generated utilizing the strengthened SEF approach offer the entropy of ~1. The execution time required to generate the cryptographic keys on different processors is also examined. The results reveal that our SEF approach is in average 1.8 times faster than existing key generation approaches which only utilize the inter pulse interval feature of ECG.