The purpose of this study was to evaluate the wrist-worn device Mio FUSE, which estimates heart rate (HR) based on photo-plethysmography, 1) in a large study group during a standardised activity, 2) in a small group during a variety of activities and 3) to investigate factors affecting HR accuracy in a real-world setting. First, 53 male participants (20 ±1 years; 1.79 ±0.07 m; 76.1 ±10.5 kg) completed a 35-km march wearing the Equivital EQ-02 as a criterion measure. Second, 5 participants (whereof 3 female; 29 ±5 years; 1.74 ±0.07 m; 67.8 ±11.1 kg) independently performed 25 activities, categorised as sitting passive, sitting active, standing, cyclic and anti-cyclic activities with the Polar H7 as a criterion device. Equivalence testing and Bland-and-Altman analyses were undertaken to assess the accuracy to the criterion devices. Third, confounders affecting HR accuracy were investigated using multiple backwards regression analyses. The Mio FUSE was equivalent to the respective criterion measures with only small systematic biases of -3.5 bpm (-2.6%) and -1.7 bpm (-1.3%) with limits of agreements of ±10.1 bpm and ±10.8 bpm during the 35-km march and during different activities, respectively. Confounding factors negatively affecting the accuracy of the Mio FUSE were found to include larger wrist size and intensified arm and/or wrist movement. The wrist-worn Mio FUSE can be recommended to estimate overall HR accurately for different types of activities in healthy adults. However, during sporting activities involving intensified arm and/or wrist movement or for detailed continuous analysis, a chest strap is preferred to the Mio FUSE to optimise HR estimation accuracy.