Background-Long-term continuous cardiac monitoring would aid in the early diagnosis and management of atrial fibrillation (AF). This study examined the accuracy of a novel approach for AF detection using photo-plethysmography signals measured from a wrist-based wearable device. Methods and Results-ECG and contemporaneous pulse data were collected from 2 cohorts of AF patients: AF patients (n=20) undergoing electrical cardioversion (ECV) and AF patients (n=40) that were prescribed for 24 hours ECG Holter in outpatient settings (HOL). Photo-plethysmography and acceleration data were collected at the wrist and processed to determine the inter-pulse interval and discard inter-pulse intervals in presence of motion artifacts. A Markov model was deployed to assess the probability of AF given irregular pattern in inter-pulse interval sequences. The AF detection algorithm was evaluated against clinical rhythm annotations of AF based on ECG interpretation. Photo-plethysmography recordings from apparently healthy volunteers (n=120) were used to establish the false positive AF detection rate of the algorithm. A total of 42 and 855 hours (AF: 21 and 323 hours) of photo-plethysmography data were recorded in the ECV and HOL cohorts, respectively. AF was detected with >96% accuracy (ECV, sensitivity=97%; HOL, sensitivity=93%; both with specificity=100%). Because of motion artifacts, the algorithm did not provide AF classification for 44±16% of the monitoring period in the HOL group. In healthy controls, the algorithm demonstrated a <0.2% false positive AF detection rate. Conclusions-A novel AF detection algorithm using pulse data from a wrist-wearable device can accurately discriminate rhythm irregularities caused by AF from normal rhythm.