Three percent diclofenac in 2.5% hyaluronan gel (DHA) is approved by the Food and Drug Administration (FDA) in the treatment of actinic keratoses (AK). We conducted a meta-analysis of the few prospective studies that evaluated the effect of DHA on the target lesion number score TLNS0 (indicating complete resolution of all target lesions in the treatment area) and/or the cumulative target lesion number score CLNS0 (indicating resolution of the target and new lesions in the treatment area) with assessment 30 days after the end of treatment. A comprehensive search of the 1966–2005 MEDLINE database and review of the reference lists of relevant articles identified the published randomised trials. Three studies were included, with a total of 364 patients. The placebo was the hyaluronan vehicule gel (HAV). The intention-to-treat analyses show that DHA significantly improve the TLNS0 (OR= 3.72; 95% CI=2.05–6.74) and the CLNS0 (OR=4.09; 95% CI=2.55–6.56) compare to HAV. Overall, 42/106 (39.6% CI: 30.8– 49.1%) had a TLNS0 with mean treatment duration of 75 days ± 21 [mean±standard deviation (SD)], and 70/179 (39.1% CI:32.3–46.4%) patients had a CLNS0 with a mean 78 days±16 treatment duration. DHA is effective compared to HAV in the treatment of AK. Further studies should establish subgroup analyses according to sites and severity of the AK lesions in order to determine if more patients could be improved in restricted indications. Biopsies, a longer follow-up evaluation, and comparisons with the other treatments of AK will also be helpful in the future to define the place of this treatment in the management of AK.