A harmonic quadrature demodulation method to extract the second harmonic component from focused ultrasound signals after a single transmit-receive event is proposed. In the proposed method, the focused ultrasound signal is converted into baseband inphase and quadrature components by multiplying with sine and cosine signals both having twice the center frequency of the transmitted signal and filtering the two modulated signals. The quadrature component is then passed through a Hilbert filter to be added to the inphase component, which leaves only the envelope of the second harmonic component. A novel phase estimation technique is employed in the proposed method to avoid the phase mismatch between the focused signal and the two modulating signals. The proposed method is verified through both theoretical analysis and computer simulations. It is shown that compared to the pulse inversion scheme the proposed method provides almost the same results for stationary targets and significantly improved harmonic to fundamental ratio for moving targets.