In the current study, a non-invasive technique for systolic blood pressure (SBP) measurement based on the detection of photoplethysmographic (PPG) pulses during pressure-cuff deflation was compared to sphygmomanometry—the Korotkoff sounds technique. The PPG pulses disappear for cuff-pressures above the SBP value and reappear when the cuff-pressure decreases below the SBP value. One hundred and twenty examinations were performed on forty subjects. In 97 examinations the two methods differed by less than 3 mmHg. In nine examinations the SBP value measured by PPG was higher than that measured by sphygmomanometry by 5 mmHg or more. In only one examination the former was lower by 5 mmHg or more than the latter. The appearance of either the PPG pulses or the Korotkoff sounds assures that the artery under the cuff is open during systolic peak pressure. In the nine examinations mentioned above the PPG pulses were observed while Korotkoff sounds were not detected, despite the open artery during systole. In these examinations, the PPG-based technique was more reliable than sphygmomanometry. The high signal-to-noise ratio of measured PPG pulses indicates that automatic measurement of the SBP by means of automatic detection of the PPG signals is feasible.