Aim This quantitative study seeks to determine why the underground organ commerce exists and thrives in Colombia, and how it responds to global donor shortages, public opposition and government initiatives to curtail it. Policy lessons and insights from the Colombian experience in organ donation and transplantation are identified in this study. Subjects and Methods Statistical random samples of 169 living and paid Colombian donors (or vendors) were apportioned between the key organ supplier cities of Bogotá and Medellín based on population. A pre-tested and interviewer-administered questionnaire was designed for organ vendors in these multistage samples. Qualitative analysis of pertinent Colombian laws and regulations forms the other half of this study. Results Survey results from Bogotá and Medellín tend to indicate shared demographic characteristics between Colombian vendors and their counterparts in developing countries that are major destinations for organ trafficking. The organ trade in Colombia is generally open, brokered and without price competition and provisions for vendors' postoperative care, which help attract many foreign buyers. These factors also increase the vulnerability of vendors to unscrupulous third parties. The study finds that public indifference, state/ institutional incapacity, corruption, and constantly changing trade environments, rules and operations subvert the legal and regulatory framework for organ donation and transplantation, which in Colombia is rather unique for its extent of coverage, complexity and detail. Conclusion The empirical evidence obtained from Bogotá and Medellín offers a challenge for governments to look beyond the availability of legal and regulatory restraints and remedies. Why and how these can be effectively undermined by organ trade participants without necessarily affecting or reversing their economic behavior are pressing issues that demand immediate attention.