We aim to determine the efficacy and safety of gene and cell angiogenic therapies in the treatment of peripheral arterial disease (PAD) and evaluate them for the first time by a meta-analysis. We include in the formal meta-analysis only the randomized placebo-controlled phase 2 studies with any angiogenic gene or cell therapy modality to treat patients with PAD (intermittent claudication, ulcer or critical ischemia) identified by electronic search in MEDLINE and EMBASE databases (1980 to date). Altogether, 543 patients are analyzed from six randomized, controlled trials that are comparable with regard to patient selection, study design, and endpoints. We perform the meta-analysis regarding clinical improvement (improvement of peak walk time, relief in rest pain, ulcer healing or limb salvage) and rate of adverse events. At the end of treatment, therapeutic angiogenesis shows a significantly clinical improvement as compared to placebo in patients with PAD (odds ratio [OR] = 1.437; 95% confidence interval [CI] = 1.03-2.00; P = 0.033). The response rate (improvement of peak walk time) of the pooled groups according to clinical severity does not significantly differ for gene therapy as compared with placebo in the treatment of claudicating patients (OR = 1.304; 95% CI = 0.90-1.89; P = 0.16). Otherwise, we find significant efficacy of the treatment in critical ischemia (OR = 2.20; 95% CI = 1.01-4.79; P = 0.046). The adverse events rates show a slightly significantly higher risk of potential nonserious adverse events (edema, hypotension, proteinuria) in the treated group (OR = 1.81; 95% CI = 1.01-3.38; P = 0.045). We find no differences in mortality from any cause, malignancy, or retinopathy. The patients with PAD, and particularly those with critical ischemia, improve their symptoms when treated with angiogenic gene and cell therapy with acceptable tolerability.