Study Design: Secondary analysis of pooled data from 3 randomized trials. Objective: This study investigated sex differences in response to physical therapy intervention for acute low back pain. Background: Sex differences in experimental pain sensitivity have been consistently described in the literature. However, clinical consequences of these sex differences have not been widely reported. Methods and Measures: Subjects (n = 165) were participants in 3 randomized trials of physical therapy interventions from outpatient physical therapy clinics in the general and military communities. Subjects were randomly assigned spinal manipulation with range-of-motion exercise, lumbar stabilization exercise, or directional-preference exercise. Outcomes were measured at 4 weeks through self-report of pain intensity and pain-related disability. Sex differences were investigated with independent t tests (baseline data), 2 × 3 analysis of variance (4-week reductions in pain and pain-related disability), and regression models (predictors of outcome). Results: Men and women had similar reductions of pain intensity (raw mean difference, 0.5; 95% CI, -1.4 to 0.4) and pain-related disability (raw mean difference, 5.3; 95% CI, -0.1 to 10.7) over 4 weeks. Baseline pain intensity, duration of symptoms, and baseline pain-related disability significantly predicted change in pain intensity for women (r 2 = 26%, P Ͻ.01). Baseline pain intensity and stabilization exercise predicted change in pain intensity for men (r 2 = 33%, P Ͻ.01). Baseline pain-related disability, duration of pain, and pain intensity predicted change in disability for women (r 2 = 24%, P Ͻ.01). Baseline pain-related disability, fear-avoidance beliefs, stabilization exercise, and leg pain predicted change in disability for men (r 2 = 32%, P Ͻ.01). Conclusion: For patients with acute low back pain, men and women had similar physical therapy outcomes for reductions in pain intensity and pain-related disability. However, men and women had different factors that predicted treatment outcome.