Study Design.: A randomized clinical trial. Objective.: To compare the effectiveness of a behavioral graded activity program with manual therapy in patients with subacute (4-12 weeks) nonspecific neck pain. Summary of Background Data.: Neck pain is a common complaint, for which many conservative therapies are available in primary care. There is strong evidence for manual therapy in combination with exercises. Psychosocial factors are also believed to play a role in chronic pain. The evidence of the effectiveness of a program focused on these factors is still unknown. Methods.: A randomized clinical trial was conducted, involving 146 patients with subacute nonspecific neck pain. The BGA program can be described as a time-contingent increase in activities from baseline toward predetermined goals. Manual therapy consists of specific spinal mobilization techniques and exercises. Primary outcomes were global perceived effect, the Numerical Rating Scale for pain and the Neck Disability Index. Secondary outcomes were the Tampa Scale for Kinesiophobia, the 4 Dimensional Symptom Questionnaire, and the Pain Coping and Cognition List. Measurements were carried out at baseline and 6, 13, 26, and 52 weeks after randomization. Data are analyzed according to the intention-to-treat principle, using multilevel analysis. Results.: The success rates at 52 weeks, based on the GPE were 89.4% for the BGA program and 86.5% for MT. This difference was not statistically significant. For pain and disability, a difference was found in favor of the BGA program; mean difference for pain = 0.99 (95% CI 0.15-1.83) and mean difference for NDI = 2.42 (95% CI 0.52-4.32). All other differences between the interventions in the primary and secondary outcomes were not statistically significant. Conclusion.: Based on this trial it can be concluded that there are only marginal, but not clinically relevant, differences between a BGA program and MT. © 2010, Lippincott Williams & Wilkins.