Early-phase trials showed the feasibility and potential efficacy of cell therapy in patients with critical limb ischemia (CLI). For systematic review, randomized controlled trials (RCTs) of cell therapy versus no cell therapy in CLI were searched from PubMed and the Cochrane library databases. Outcome measures included major amputation, complete ulcer healing, ankle-brachial index (ABI), and all-cause mortality. Data were pooled using 16 RCTs, involving 774 patients. Compared with no cell therapy, cell therapy significantly reduced major amputation (odds ratio [OR]: 0.54; 95% CI: 0.34-0.87: P = .01) and improved ulcer healing (OR: 2.90; 95% confidence interval [CI]: 1.44-5.82; P < .01) and ABI (OR: 5.91; 95% CI: 1.85-18.86: P < .01). Peripheral blood-derived mononuclear cells (PB-MNCs; OR: 0.29; 95% CI: 0.12-0.72; P < .01) and bone marrow concentrate (OR: 0.44; 95% CI: 0.21-0.93; P = .03) significantly lowered the risk of major amputation. The PB-MNCs also significantly increased ulcer healing (OR: 5.77; 95% CI: 1.77-18.87; P < .01). All-cause mortality was similar in both groups (OR: 0.78; 95% CI: 0.44-1.40; P = .41). However, all estimates were nonsignificant following reanalysis using placebo-controlled RCTs only. Cell therapy remains a potential therapeutic option in CLI, but further larger placebo-controlled RCTs are needed.