The post-organ transplant immunosuppressive therapy includes the administration of tacrolimus (Tac) or cyclosporine (CsA), along with antimetabolites (Antim) or mTOR inhibitors, with or without prednisone. A survey was conducted to investigate clinical experience regarding the use, efficacy, safety profile, and determinants of choice of maintenance immunosuppressive therapies. The questionnaire was sent to healthcare workers of 45 transplant centers specializing in kidney (K), liver (L), heart (H), and lung (P) transplants. Seventy-one responses were received from 15 Italian regions. The indicated first-choice therapy was Tac + Antim, except in the hepatic field where Tac monotherapy was favored. According to 44.1% of respondents, the first-choice therapy has changed over the last 15 years due to the replacement of CsA with Tac and increased use of mTOR inhibitors. Regarding the determinants of the index therapy, the choice of schemes to be applied depends mainly on international guidelines, previous experience, and internal protocols within the facility (80.3%; 54.9%; 50.7%, respectively). Compared to standard therapy, the criteria guiding the prescription of different therapies mainly involve the presence of comorbidities (K: 81.3%; L: 88.2%; H: 73.3%; P: 85.7%) and the evaluation of specific clinical parameters of the recipient. Additionally, the majority of respondents are in favor of using generic versions where available. The survey reveals dimensions not detectable by current healthcare administrative flows; such integrations provide a broader picture of the factors influencing the choice of post-transplant immunosuppressive therapeutic schemes.