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Purpose: Different types of activities have independent and additive benefits for adult health. This study intended to assess the association between aerobic activity and muscle-strengthening activities and health-related quality of life (HRQoL) and physical and mental health in patients with neck pain. Methods: This cross-sectional study included data on patients with neck pain from the National Health and Nutrition Examination Survey (NHANES) dataset between 2001 and 2004. Weighted logistic regression analyses were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) for the associations between aerobic activity, muscle-strengthening activities, and their combination, and HRQoL, physically unhealthy days (≥ 14 days/month), and mentally unhealthy days (≥ 14 days/month). Subgroup analyses were performed according to age, gender, and screen time. Results: A total of 794 patients with neck pain were included, of whom 504 had good HRQoL and 290 had poor HRQoL. Aerobic activity (OR=0.35, 95% CI: 0.21– 0.57) and muscle-strengthening activities (OR=0.50, 95% CI: 0.26– 0.98) were associated with good HRQoL in patients with neck pain, but only aerobic activity (OR=0.42, 95% CI: 0.28– 0.63) was linked to shorter physical unhealthy days. No associations were found between aerobic activity, muscle-strengthening activities, and mentally unhealthy days (P 0.05). The trends for the combined result of aerobic activity and muscle-strengthening activities on HRQoL, physically unhealthy days, and mentally unhealthy days were significant (Ptrend< 0.001). Subgroup analyses found that the combined result of aerobic and muscle-strengthening activities was only more significant on HRQoL in patients aged < 60 years or ≥ 60 years, males or females, and patients with screen time < 3 hours or ≥ 3 hours (Ptrend< 0.05). Conclusion: Aerobic and muscle-strengthening activities were associated with good prognosis in patients with neck pain, but the effect of aerobic activity may be more pronounced. [ABSTRACT FROM AUTHOR]