There is increasing evidence that pain-related fear influences the development and maintenance of pain disability, presumably mediated through the fear-related avoidance of valued activities. Individually tailored graded exposure in vivo (GEXP) has been demonstrated to reduce pain-related fear and increase functional abilities in patients with chronic low back pain, neck pain, and complex regional pain syndrome. The current study aimed to test whether these effects generalize towards patients with work-related upper extremity pain. A sequential replicated and randomized single-case experimental phase design with multiple measurements was used. Within each participant, GEXP was compared to a no-treatment baseline period and a no-treatment 6-month follow-up period. Eight patients who reported a high level of pain-related fear were included in the study. Daily changes in pain catastrophizing, pain-related fear, and pain intensity were assessed using a diary, and subjected to randomization tests. Before the start of the baseline period, just after GEXP, and at 6-month follow-up, clinically relevant changes of pain catastrophizing, pain-related fear, perceived harmfulness of physical activity, pain disability, and participation/autonomy were verified. When GEXP was introduced, levels of pain catastrophizing and pain-related fear decreased significantly. Clinically relevant improvements were observed for pain disability, perceived participation, and autonomy. These favourable changes were maintained until 6-month follow-up. The findings of the current study underscore the external validity of a cognitive-behavioural GEXP treatment for patients with chronic pain reporting increased pain-related fear.