OBJECTIVES: In investigator-based clinical trials, the use of placebo is often justified as it increases the probability from the peers’ expertise of 1/ gaining a public grant; 2/ publishing results in higher-rank journals. METHODS: Among the 139 randomized clinical trials (RCT) evaluating drugs and currently managed by the Paris Hospitals, 68 are placebo-controlled. Aim is to analyze the hurdles in obtaining the placebo and its justification. RESULTS: Half of the studies had difficulties in obtaining the placebo. In rare cases, the study was unfeasible. When the placebo concerns a new drug, the company may accept to provide the drug and its placebo, at the eventual expense for the institutional sponsor to provide all the data without any further compensation. It may be considered as a disguised industrial sponsorship, the institutional sponsor while taking the responsibility of the study, being relegated to a role of a CRO. Obtaining a placebo of an old drug is trickier since the company may not sell anymore its product and generic companies are not able and/or interested to manufacture the placebo. The request of a manufacturer can be so expensive (up to 200.000€) that is exceeds by far the price of the verum, and of the grant. The rationale for using a placebo as comparator is to ensure a double-blind. However, when the drug administration is short (e.g. emergency setting), or when the endpoint is “hard” (i.e. mortality, imaging, biology), it is unlikely that any placebo effect from subjects and/or investigators may impact the endpoint assessment. In such situations, the comparator may be “no treatment” with whenever possible a blind assessment. CONCLUSIONS: Placebo-controlled RCT are challenging for institutional sponsors. Investigators and methodologists when writing a protocol and peers’ expertise of a grant or a publication submission should consider the necessity and the feasibility of placebo.