He worked very closely with Hetherington and when he was imprisoned for publishing an unstamped newspaper, O'Brien took over the editorship of The Poor Man's Guardian.
During this period, Henry Hetherington and O'Brien led the struggle against the stamp duty and were consistent in their arguments that working people needed cheap newspapers that contained political information.
O'Brien became fascinated with the history of radicalism and began work on books on Robespierre, the French Revolution and the English Commonwealth.
In 1838 O'Brien added his support for a more militant approach to winning the vote that was being advocated by Feargus O'Connor and George Julian Harney through the London Democratic Association.
O'Brien continued to be active in the Chartist movement and in 1840 he was arrested and charged with making a seditious speech in Manchester.
O'Brien finally broke with O'Connor when along with Henry Vincent and Robert Gammage he joined the Complete Suffrage Union.
He also gave public lectures and in 1851 he opened the Eclectic Institute in Denmark Street, Soho, London, where adult education classes were offered in English, French, science and mathematics.
He suffered from bronchitis and his Chartist friends attempted to raise money in recognition of the great sacrifices that he had made in the struggle to win universal suffrage and the freedom of the press.