Context: Osteopathic manipulative treatment (OMT) is often used to treat patients with low back pain (LBP). Objective: To identify subgroups of patients with chronic LBP who achieve medium to large treatment effects with OMT based on responder analyses involving pain and functioning outcomes from the OSTEOPAThic Health outcomes In Chronic low back pain (OSTEOPATHIC) Trial. Methods: This randomized, double-blind, sham-controlled trial involving 455 pa- tients in Dallas-Fort Worth was conducted from 2006 to 2011. A 100-mm visual ana- log scale (VAS) for LBP intensity and the Roland-Morris Disability Questionnaire (RMDQ) for back-specific functioning were used to assess primary and secondary outcomes, respectively. Substantial improvement was defined as 50% or greater reduction at week 12 compared with baseline. Cumulative distribution functions for the RR and number-needed-to-treat (NNT) were used to assess response. Results: Medium treatment effects for LBP intensity were observed overall (RR, 1.41; 95% CI, 1.13-1.76; P=.002; NNT, 6.9; 95% CI, 4.3-18.6). However, large treatment effects were observed in patients with baseline VAS scores of 35 mm or greater. Although OMT was not associated with overall substantial improvement in back-specific functioning, patients with baseline RMDQ scores of 7 or greater experienced medium effects, and patients with baseline scores 16 or greater expe- rienced large effects that were significant. The OMT effects for LBP intensity and back-specific functioning were independent of baseline patient demographic charac- teristics, comorbid medical conditions, and medication use for LBP during the trial. Conclusions: Subgrouping according to baseline levels of chronic LBP inten- sity and back-specific functioning appears to be a simple strategy for identifying sizeable numbers of patients who achieve substantial improvement with OMT and may thereby be less likely to use more costly and invasive interventions.