Chronic leg ulcers are a debilitating, often painful, and costly condition. Leg ulcer healing may be impaired by bacterial colonization, which, unless effective intervention is instigated, can lead to infection. Although it is generally agreed that an antimicrobial dressing is clinically indicated when a wound becomes critically colonized, there is currently no agreement on what constitutes the best practice in the use of antimicrobials. This research compared the effectiveness of two commonly used antimicrobials: nanocrystalline silver and cadexomer iodine. A randomized-controlled trial was conducted in which 281 community nursing clients with leg ulcers compromised by bacterial burden were randomly assigned to have their wounds treated with either silver or iodine dressings. Sixty-four percent of ulcers healed within 12 weeks. The performance of each of the two antimicrobials was comparable in terms of overall healing rate and the number of wounds healed. However, use of silver compounds was associated with a quicker healing rate during the first 2 weeks of treatment and in wounds that were larger, older, and had more exudate. This trial provides some insights as to circumstances in which one product may be preferred over the other.