Puffy nipples occur when one or both nipples and the surrounding areola are swollen or enlarged. However, the most common cause of puffy nipples is related to hormone imbalances, specifically a condition known as gynecomastia. Prescription medications: Sometimes, prescription medications can cause puffy nipples. How To Prevent Puffy NipplesResearch suggests about 30-65% of males will experience puffy nipples at some point in their lives. You can reduce the likelihood of puffy nipples from other causes by eating a nutritious diet, exercising regularly, and avoiding drug and alcohol use.