BACKGROUND: Wearable devices using photo-plethysmography (PPG) can accurately detect heart beats and may be useful for heart rate measurement and diagnosis of arrhythmias such as atrial fibrillation (AF). A previous study of a new portable PPG sensor (CardiacSense) showed high accuracy in heart rate measurement and AF detection in resting patients. We report a trial done to test the same device in active ambulatory patients with diverse characteristics. METHODS: A cohort of 24 ambulatory volunteers, underwent simultaneous PPG recording and continuous electrocardiogram (ECG) recording under different environmental conditions and situations. Per study protocol, the subjects were diverse in age, BMI, hair density and skin tone. Four subjects had AF. Heart rate measurement using the PPG device was compared to measurements by ECG. RESULTS: Of 163,527 recorded ECG-detected beats in the trial, 86,929 (53.2%) were also recorded by the PPG device. Most undetected heart beats were due to motion induced noise. Correlation between ECG and PPG was high (R = 0.94, p < 0.0001), yet in subjects with AF correlation was lower (R = 0.80, p < 0.0001). A Bland-Altman analysis showed the mean difference between measurements was -0.7 ms (95% limit of agreement -93.8 to 92.2). A total of 86,217 (99.9%) of all RR measurements were reliably measured (RR difference within 100 ms). Reliability was sustained (>99.8%) in subjects of all groups including subjects with AF. CONCLUSIONS: This study showed that, in the absence of movement-related noise, the CardiacSense PPG device can reliably detect HR in a variety of situations and subjects' characteristics.