The overall objective of this study is to evaluate the effectiveness of dehydrated human amnion/ chorion membrane (dHACM) in reducing time to complete wound closure in patients with venous leg ulcers (VLUs).

Inclusion Criteria:

1. Index ulcer characteristics:

   1. Full-thickness venous leg ulcer for ≥ 30 days
   2. Ulcer area after debridement is ≥ 1 cm² and ≤ 25 cm² at the randomization visit
   3. Has a clean, granulating base with minimal adherent slough

2. Subject has completed 14 day run-in period with ≤ 25% wound area reduction post-debridement.

3. Have one of the following:

   • Ankle Brachial Pressure Index (ABI) > 0.75. (Calculations will be made using measurements from both posterior tibial and dorsalis pedis arteries as well as both arms) OR
   • Have venous insufficiency confirmed by duplex ultrasound examination for valvular or venous incompetence.

4. Age ≥ 18.

5. Females of childbearing potential must be willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence).

6. Ability to read/understand and sign Informed Consent and Release of Medical Information Forms.

7. Ability to understand and comply with weekly visits and follow-up regimen.

Exclusion Criteria:

1. Index Ulcer Assessment - Index ulcer meeting the following criteria will not be eligible for enrollment:

   1. Penetrates down to muscle, tendon, or bone
   2. Presence of another venous ulcer ≤ 2 cm from index ulcer
   3. Is deemed by the Investigator to be caused by a medical condition other than venous insufficiency
   4. Exhibits clinical signs and symptoms of infection
   5. If in the opinion of the Investigator, the wound is suspicious for cancer, the subject should undergo an ulcer biopsy to rule out carcinoma. If carcinoma is ruled out, the subject may be re-screened.
   6. Located on the dorsum of the foot or with more than 50% of the ulcer below the malleolus

2. Prior therapies - Subjects receiving treatment with any of the following will not be eligible for enrollment:

   1. In the last 7 days - Negative pressure wound therapy of the index ulcer
   2. In the last 7 days - Hyperbaric oxygen therapy
   3. In the last 30 days - Treatment with cytotoxic chemotherapy, application of topical steroids to the ulcer surface, or use of ≥ 14 days of immune-suppressants (including systemic corticosteroids); or, subject is anticipated to require such medications during the course of the study
   4. In the last 30 days - study ulcer treatment with any advanced therapy, including EpiFix®, tissue engineered materials (e.g. Apligraf® or Dermagraft®), or other scaffold materials (e.g. OASIS® Wound Matrix, MatriStem® Wound Matrix)
   5. In the last 30 days - Subject has been on any investigational drug(s) or therapeutic device(s)
   6. In the last 8 weeks - Amputation or revascularization (surgical or stenting) to the affected leg
   7. Any history of radiation at the ulcer site
   8. Any prior participation in a MiMedx® study
   9. Study ulcer has undergone ≥ 12 months of continuous high strength compression therapy over its duration

3. Subject criteria that will make subject ineligible for enrollment:

   1. Known osteomyelitis or active cellulitis at wound site
   2. Hemoglobin A1C >12 in the last 60 days prior to randomization
   3. Active malignant disease or subject is less than 1 year disease-free
   4. NYHA Class III and IV congestive heart failure (CHF), as defined by the following criteria: Class III: Symptoms with moderate exertion; Class IV: Symptoms at rest
   5. Auto-immune disorders including Systemic Lupus Erythematosus (SLE), Fibromyalgia, Acquired Immunodeficiency Syndrome (AIDS) or HIV
   6. Allergy or known sensitivity to Aminoglycosides such as gentamicin sulfate and/or streptomycin sulfate
   7. Known allergy to the components of the multi-layer compression bandaging, or who cannot tolerate MLCT
   8. Presence of any condition (including current drug or alcohol abuse, medical or psychiatric condition) that is likely to impair understanding of or compliance with the study protocol in the judgment of the Investigator
   9. Pregnancy at enrollment or within last 6 months, women who are breastfeeding, or women of childbearing potential who are planning to become pregnant during the time of the study OR are unwilling/unable to use acceptable methods of contraception (birth control pills, barriers, or abstinence)