Criminal trials and claims against physicians for malpractice-related damages have increased dramatically in recent years, and, with Obstetrics and Gynecology being one of the medical specialties that is at the highest risk, we carried out a retrospective analysis aimed at examining all Obstetrics- and Gynecology-related medical professional liability prosecutions within the General Register of Criminal Records of the Rome Public Prosecutor’s Office between the years 2000 and 2014. The number of prosecutions increased steadily in the years 2000–2005, with varying trends in the following years. A total of 727 healthcare professionals were involved in criminal charges, and most prosecuted crimes were related to Articles 590 and 589 of the Italian Penal Code, followed by violations of Article 17 of Law 194/78. In most cases, filing was requested and granted without opposition. In 95 cases, an expert witness was appointed by the Court, and in 68 cases, the technical consultants of the State Prosecutor found culpable conduct. Public hospitals, private nursing homes and outpatient clinics, or private practices were mostly involved; in 45% of the cases, the physicians were hospital employees. In this setting, Italy is prepared to introduce new measures and regulations to address the issues posed by defensive medicine and charges of professional liability for healthcare providers.