Abstract Objective To investigate systematically the presence of the Babinski sign in paintings of the Christ Child by the greatest painters of the Renaissance. Design Observational analysis. Setting Large collection of paintings depicting the Christ Child from Flemish, Rhenish, and Italian schools between 1400 and 1550 CE, searched using published catalogues and Google. Study sample 302 Renaissance paintings (by 19 painters) depicting the Christ Child. Main outcome measure Babinski sign, defined as a hallux extension with an amplitude greater than 30°. The presence of foot sole stimulation was also noted. Results An unquestionable upgoing toe was apparent in 90 (30%) of the 302 paintings. The Babinski sign was present in more than 60% of Christ Child paintings by Rogier van der Weyden, Hans Memling, Martin Schongauer, and Matthias Grünewald. A bilateral Babinski sign was observed in three paintings. Stimulation of the sole was noted in 48/90 (53%) paintings and was always present in paintings by Andrea del Verrocchio, Leonardo da Vinci, and Giorgione. No association existed between the presence of the Babinski sign and the period during which the painter was active. Conclusions Four main factors were noted in relation to the representation of the Babinski sign in paintings of the Christ Child: the physiological toe phenomenon in infants, the representation of the nudity of the Christ by painters during the 15th century to demonstrate the incarnation, Renaissance painters’ need for precise observation of anatomy, and the desire of some Rhenish and Flemish painters to depict very realistic details. Italian Renaissance painters, whether Mannerist or not, tended to idealise the beauty of human body, and they often did not reproduce the Babinski sign.