Twenty-six (26) randomized controlled trials were included in this systematic review and meta-analysis evaluating the efficacy of spinal manipulative therapy (SMT) compared to either active control comparators or sham treatment in the management of acute low back pain. Observational studies were also included to evaluate the safety of SMT. Results demonstrated significant effects in favour of SMT at 3-6 weeks for both pain and function. Eight of the 26 RCTs from the efficacy analyses were included in comparison of adverse events, and complemented by another 3 RCTs and 5 prospective cohort studies which only reported data on adverse events. There was high-quality evidence that transient musculoskeletal pain adverse events may be experienced following SMT, though a few studies which compared rates between treatment groups suggested similar incidences between manual therapy with and without SMT, or between SMT and sham treatment. No serious adverse events were reported among RCTs.