Background context: Several conservative therapies have been shown to be beneficial in the treatment of chronic low back pain (CLBP), including different forms of exercise and spinal manipulative therapy (SMT). The efficacy of less time-consuming and less costly self-care interventions, for example, home exercise, remains inconclusive in CLBP populations. Purpose: The purpose of this study was to assess the relative efficacy of supervised exercise, spinal manipulation, and home exercise for the treatment of CLBP. Study design/setting: An observer-blinded and mixed-method randomized clinical trial conducted in a university research clinic in Bloomington, MN, USA. Patient sample: Individuals, 18 to 65 years of age, who had a primary complaint of mechanical LBP of at least 6-week duration with or without radiating pain to the lower extremity were included in this trial. Outcome measures: Patient-rated outcomes were pain, disability, general health status, medication use, global improvement, and satisfaction. Trunk muscle endurance and strength were assessed by blinded examiners, and qualitative interviews were performed at the end of the 12-week treatment phase. Methods: This prospective randomized clinical trial examined the short- (12 weeks) and long-term (52 weeks) relative efficacy of high-dose, supervised low-tech trunk exercise, chiropractic SMT, and a short course of home exercise and self-care advice for the treatment of LBP of at least 6-week duration. The study was approved by local institutional review boards. Results: A total of 301 individuals were included in this trial. For all three treatment groups, outcomes improved during the 12 weeks of treatment. Those who received supervised trunk exercise were most satisfied with care and experienced the greatest gains in trunk muscle endurance and strength, but they did not significantly differ from those receiving chiropractic spinal manipulation or home exercise in terms of pain and other patient-rated individual outcomes, in both the short- and long-term. Conclusions: For CLBP, supervised exercise was significantly better than chiropractic spinal manipulation and home exercise in terms of satisfaction with treatment and trunk muscle endurance and strength. Although the short- and long-term differences between groups in patient-rated pain, disability, improvement, general health status, and medication use consistently favored the supervised exercise group, the differences were relatively small and not statistically significant for these individual outcomes.