The purpose of this study is to evaluate the safety and efficacy of trifarotene 50 microgram per gram (mcg/g) cream compared to its vehicle on the risk of formation of atrophic acne scars after 24 weeks of treatment in facial acne participants assessed by atrophic acne scars count.

Key Inclusion Criteria:

• Participant with clinical diagnosis of acne vulgaris on the face as defined by (excluding the nose and middle zone of approximately 2 centimeter [cm]):

  1. Investigator's Global Assessment (IGA) score of 3 (Moderate) or 4 (Severe), with the same score on both sides of the face; and
  2. A minimum of 20 inflammatory lesions (papules and pustules) in total with at least 10 on each side; and
  3. No more than 2 nodules (greater than or equal to [>=] 1 cm in diameter) on the face; and
  4. A minimum of 10 atrophic acne scars in total (>2 mm)

• Participant with a symmetrical number of the following lesions/scars on the whole face:

  1. Inflammatory and non-inflammatory lesions; and
  2. Atrophic acne scars (minimum of 4 scars per half-face)

• The participant is a female of non-childbearing potential

• If a female of childbearing, potential uses oral contraceptives that are also approve for treating acne vulgaris

• Other protocol defined inclusion criteria could apply

Key Exclusion Criteria:

• Participant with acne conglobata, acne fulminans, secondary acne, nodulocystic acne and acne requiring systemic treatment
• Participant with any acne cyst on the face or with more than 3 excoriated acne lesions
• Participant with known active or chronic allergies or suspected allergy to trifarotene or excipients of the formulation
• Participant with facial dermal conditions (for example, tattoo, skin abrasion, eczema, sunburned skin, scars, nevi, etc.) that may interfere with study assessments in the opinion of the investigator
• Participant with known impaired hepatic or renal functions, based on medical history