Vasari writes about the painting: "In the church of the Innocenti he painted in tempera a much-admired picture of the Magi, containing some fine heads and varied physiognomies of people both young and old, notably a head of the Virgin, displaying all the modesty, beauty and grace which art can impart to the Mother of God".

There are so many saints in this Adoration that it is not easy to make out the three Magi. On the left, Saint John the Baptist is kneeling and pointing to the Madonna. The orphans of the Spedale are represented by two of the innocent boys who were killed during the Slaughter of the Innocents in Bethlehem, kneeling in the foreground. There are gaping bloody wounds to their faces, arms and necks.

In this Adoration of the Magi, Ghirlandaio's carefully thought out use of colour is particularly impressive: Ghirlandaio distributes the glowing colours evenly. Mary in the centre is wearing a blue cloak over a red dress. The oldest king kneeling in front of her is wearing a variation of these colours combined with yellow. To the left of Mary, the youngest king holding the valuable goblet in his hand - he almost looks like Saint John the Evangelist - is also dressed in blue, yellow and red. The figure standing on the right edge of the picture wearing an expensive hat repeats this combination of colours, though now the blue and yellow are reversed. In the second figure from the right, wearing the blue hat, the Madonna's colours of red and blue are visible again, and they are repeated in clothes of the bearded man wearing a turban on the left edge of the picture. Between the Madonna and the man with the blue hat on the right, the artist creates a yellow highlight, though with a weaker blue accent, in the figure of Joseph. This row of figures alone produces a rhythm of colour from left to right: red and blue; yellow, blue and red; red and blue; yellow and blue; red and blue; yellow, blue and red.

The work represents one of Ghirlandaio's most important "easel" works. Here too the assistants were at work. Indeed, in the scene of the Slaughter of the Innocents in the background, Berenson recognized the hand of Bartolomeo di Giovanni, the author of the stories from the predella.