In 622 C.E. Uthman migrated with his wife Ruqayya to Madina. They were in the third batch of the Muslims who migrated to Madina. Their companions on the migration included Akasha bin Muhsin, Zainab b Jahsh, and her sisters Hamna and Umm Habiba. On arrival in Madina Uthman stayed with Aus b Thabit Ansari of the Najjar tribe. After some time Uthman purchased a house of his own and shifted there.

The world of Madina was quite different from the world of Makkah. At Makks.h the Muslims were a persecuted people, at Madina they were the masters of their destiny. The life at Madina was a great break with the past. The days of trials, tribulations and tortures were now over; in the new life at Madina the Muslims were set on the path of fulfillment To rehabilitate the immigrants from Makkah in the society of Madina the Holy Prophet established a fraternity among the Muslims from Makkah and the Muslims of Madina, hereunder each immigrant was paired with an Ansar of corresponding status. The brotherhood thus established was unique in the annals of mankind. So strong and cordial were these bonds that they even surpassed the relationship of blood. The Ansars helped their immigrant brothers liberally. Uthman did not stand in need of any financial help from his Ansar brother. He was one of the richest merchants of Makkah, and had amassed considerable fortune. He brought all such fortune with him to Madina. In Madina the Muslims were generally agriculturists and were not very much interested in trade. The trade of the town was in the hands of the Jews. There was thus considerable scope for the Muslims in promoting trade. Uthman took advantage of this position and established himself as a trader in Madina. He worked hard and honestly, and his business flourished. Soon he became one of the richest men in Madina as he had been one of the richest merchants in Makkah.