Abstract Cardiovascular diseases are associated with high morbidity and mortality. However, it is still a challenge to diagnose them accurately and efficiently. Electrocardiogram (ECG), a bioelectrical signal of the heart, provides crucial information about the dynamical functions of the heart, playing an important role in cardiac diagnosis. As the QRS complex in ECG is associated with ventricular depolarization, therefore, accurate QRS detection is vital for interpreting ECG features. In this paper, we proposed a real-time, accurate, and effective algorithm for QRS detection. In the algorithm, a proposed preprocessor with a band-pass filter was first applied to remove baseline wander and power-line interference from the signal. After denoising, a method combining K-Nearest Neighbor (KNN) and Particle Swarm Optimization (PSO) was used for accurate QRS detection in ECGs with different morphologies. The proposed algorithm was tested and validated using 48 ECG records from MIT-BIH arrhythmia database (MITDB), achieved a high averaged detection accuracy, sensitivity and positive predictivity of 99.43, 99.69, and 99.72%, respectively, indicating a notable improvement to extant algorithms as reported in literatures.