Atrial fibrillation (AF) can be detected by analysis of the rhythm of heartbeats. The development of photoplethysmography (PPG) technology has enabled comfortable and unobtrusive physiological monitoring of heart rate with a wrist-worn device. Therefore, it is important to examine the possibility of using PPG signal to detect AF episodes in real-world situations. The aim of this paper is to evaluate an AF detection method based on artificial neural networks (ANN) from PPG-derived beat-to-beat interval data used for primary screening or monitoring purposes. The proposed classifier is able to distinguish between AF and sinus rhythms (SR). In total 30 patients (15 with AF, 15 with SR, mean age 71.5 years) with multiple comorbidities were monitored during routine postoperative treatment. The monitoring included standard ECG and a wrist-worn PPG monitor with green and infrared light sources. The input features of the ANN are based on the information obtained from inter-beat interval (IBI) sequences of 30 consecutive PPG pulses. One of the main concerns about the PPG signals is their susceptibility to be corrupted by noise and artifacts mostly caused by subject movement. Therefore, in the proposed method the IBI reliability is automatically evaluated beforehand. The amount of uncertainty due to unreliable beats was 15.42%. The achieved sensitivity and specificity of AF detection for 30 beats sequences were 99.20 ± 1.3 and 99.54 ± 0.64, respectively. Based on these results, the ANN algorithm demonstrated excellent performance at recognizing AF from SR using wrist PPG data.