IMPORTANCE: Existing guidelines and systematic reviews lack clear recommendations for prevention of low back pain (LBP). OBJECTIVE: To investigate the effectiveness of interventions for prevention of LBP. DATA SOURCES: MEDLINE, EMBASE, Physiotherapy Evidence Database Scale, and Cochrane Central Register of Controlled Trials from inception to November 22, 2014. STUDY SELECTION: Randomized clinical trials of prevention strategies for nonspecific LBP. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the risk of bias. The Physiotherapy Evidence Database Scale was used to evaluate the risk-of-bias. The Grading of Recommendations Assessment, Development, and Evaluation system was used to describe the quality of evidence. MAIN OUTCOMES AND MEASURES: The primary outcome measure was an episode of LBP, and the secondary outcome measure was an episode of sick leave associated with LBP. We calculated relative risks (RRs) and 95% CIs using random-effects models. RESULTS: The literature search identified 6133 potentially eligible studies; of these, 23 published reports (on 21 different randomized clinical trials including 30,850 unique participants) met the inclusion criteria. With results presented as RRs (95% CIs), there was moderate-quality evidence that exercise combined with education reduces the risk of an episode of LBP (0.55 [0.41-0.74]) and low-quality evidence of no effect on sick leave (0.74 [0.44-1.26]). Low- to very low-quality evidence suggested that exercise alone may reduce the risk of both an LBP episode (0.65 [0.50-0.86]) and use of sick leave (0.22 [0.06-0.76]). For education alone, there was moderate- to very low-quality evidence of no effect on LBP (1.03 [0.83-1.27]) or sick leave (0.87 [0.47-1.60]). There was low- to very low-quality evidence that back belts do not reduce the risk of LBP episodes (1.01 [0.71-1.44]) or sick leave (0.87 [0.47-1.60]). There was low-quality evidence of no protective effect of shoe insoles on LBP (1.01 [0.74-1.40]). CONCLUSION AND RELEVANCE: The current evidence suggests that exercise alone or in combination with education is effective for preventing LBP. Other interventions, including education alone, back belts, and shoe insoles, do not appear to prevent LBP. Whether education, training, or ergonomic adjustments prevent sick leave is uncertain because the quality of evidence is low.