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There is a serious need to provide effective early interventions that prevent the development of persistent pain and disability. Identifying patients at risk for this development is an important step. Our aim was to explore whether distinct subgroups of individuals with similar response patterns on a screening questionnaire exist. Moreover, the objective was to then relate these groups to future outcomes, for example, sick leave as an impetus for developing tailored interventions that might better prevent chronic problems. A total of 363 patients seeking primary care for acute or subacute spinal pain completed the Örebro Musculoskeletal Pain Screening Questionnaire and were then followed to determine outcome. Cluster analysis was used to identify subgroups. Validity was tested using 3 methods including the split-half technique. The subgroups were compared prospectively on outcome measures obtained 1 year later. Using pain intensity, fear-avoidance beliefs, function, and mood, we found 4 distinct profiles: Fear-Avoidant, Distressed Fear-Avoidant, Low Risk, and Low Risk-Depressed Mood. These 4 subgroups were also robust in all 3 of the validity procedures. The 4 subgroups were clearly related to outcome. Although the low risk profiles had virtually no one developing long-term sick leave, the Fear-Avoidant profile had 35% and the Distressed Fear-Avoidant profile 62% developing long-term sick leave. Our results suggest that fear-avoidance and distress are important factors in the development of pain-related disability and may serve as a key for early identification. Providing interventions specific to the factors isolated in the profiles should enhance the prevention of persistent pain and disability.