Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been described in blood samples from large series of patients. Its prevalence and consequences remain questioned because sequencing methods vary and because most studies were performed in cohorts of individuals suffering from non-hematological diseases (solid cancers, diabetes, cardiovascular or psychiatric diseases). CHIP has been described as a risk factor for blood cancer. However, the diagnosis of most blood cancers relies on morphologic and genetic examination of the bone marrow, and clonal hematopoiesis has never been evaluated in bone marrow samples from healthy individuals. Hence, it is not clear whether the current definition of CHIP is clinically relevant. To address this issue, we studied clonal hematopoiesis in paired peripheral blood and bone marrow samples from an unprecedented cohort of rigorously selected healthy volunteers. Methods: Here, we investigated the frequency of clonal hematopoiesis in 82 paired bone marrow and blood samples from carefully selected healthy adult volunteers (HEALTHOX clinical trial, ClinicalTrials.gov Identifier: NCT02789839). This study was approved by the ethics committees (CPP Tours and AFSSAPS identifier ID-RCB: 2011-A00262-39; CPP Ile-de-France III: 2753). Forty-one genes known to be mutated in myeloid malignancies were sequenced with a 1% threshold of detection. All variants were checked using IGV software v2.3. Statistical analyses were performed using Mann-Whitney, chi-squared, Fisher’s exact, Wilcoxon matched-pairs tests or Spearman correlation using GraphPad Prism 6. Results: In bone marrow samples, clones were found in almost 40 % of healthy volunteers over 50 years-old (yo). The most frequent mutations were found in DNMT3A (48%) and TET2 (28%) and the other mutations were found in ASXL1 (8%), JAK2 (8%), RAD21 (4%) and SRSF2 (4%) with one individual carrying three variants. Blood parameters and bone marrow smears were normal with the exception of two individuals with mild macrocytosis or thrombocytosis. Clonal hematopoiesis cases differed from others by age (62.8 vs. 38.6 years, P < .0001) and platelet count (294 vs. 241 G/L, P < .0208). Conclusions: These results confirm that clonal hematopoiesis is a very common condition in healthy adults over 50 years old. Consequently, the detection of driver myeloid mutations should be interpreted with caution in the absence of cytologic abnormalities in the blood and/or in the bone marrow.