Objective. To identify subgroups of workers absent from work due to low back pain who are more or less likely to return to work earlier as a result of a graded activity intervention, and to investigate whether this intervention is effective in reducing pain-related fears and if so, whether these reductions in pain-related fears mediate return to work. Methods. A subgroup analysis was conducted on data from a previous randomized controlled trial of 134 Dutch airline workers, which found that a behaviorally-oriented graded activity intervention was more effective than usual care in stimulating return to work. The subgroup analyses added interaction terms to a Cox regression model that described the relationship between treatment allocation and return to work over 12 months of followup. Furthermore, we studied the effects of graded activity on pain-related fears and added variables indicating a reduction in pain-related fears to the model in order to investigate their influence on return to work. Results. Statistically significant interactions were found for disability, fear-avoidance beliefs about physical activity, and fear-avoidance beliefs about work. No indication was found that the reduction in pain-related fears in the graded activity group mediated more favorable return-to-work results in this group. Conclusion. Workers who perceive their disability to be moderate and workers with moderate scores for fear-avoidance beliefs return to work more rapidly as a result of the graded activity intervention than workers with higher scores. The return to work of workers receiving the graded activity intervention is possibly independent from the reductions in pain-related fears caused by this intervention. © 2008, American College of Rheumatology.