He started his own practice in 1816. In 1825 he formed a partnership with John Miller which lasted until 1847. Their firm operated from the ground floor of Grainger's house at 56 George Street, in the centre of Edinburgh's New Town.
Between 1845 and 1849 he was engaged on the difficult tasks of digging the Bramhope Tunnel and building the Arthington Viaduct as part of laying the Leeds to Stockton-on-Tees line. The first modern rail ferry, the Leviathan, was designed in 1849 by Grainger for the Edinburgh, Perth and Dundee Railway to cross the Firth of Forth between Granton and Burntisland. The service commenced on 3 February 1850.
Projects he was involved in included many railway bridges, viaducts and tunnels, including work on the Monkland and Kirkintilloch Railway, Ballochney Railway, Garnkirk and Glasgow Railway, Wishaw and Coltness Railway, Paisley and Renfrew Railway, Dundee and Arbroath Railway, Arbroath and Forfar Railway, and the Leeds Northern Railway, where he was chief engineer at the time of his death.
He married Jessie Fraser (1809-1880) around 1843. They had two daughters: Frances and Agnes, both of whom died young. They are all buried with him.
- New sea-wall at Newhaven Harbour (1837)
- Broughty Ferry railway station (1838)
- Haymarket Station, Edinburgh (1840) with David Bell
- Bridge at Russell Place in Edinburgh (1843)
- North Leith Railway Station (1845) demolished despite being an architectural gem and the prototype of all future railway stations
- Railway bridge at Warriston, Edinburgh (1845)
- Cupar railway station (1846)
- Ladybank railway station (1847)
- Burntisland railway station (1847)
- Subterranea Britannica
- Railscot entry, Thomas Grainger
- The Gentleman's Magazine, obituary, Google books
- The Civil Engineer and Architect's Journal, obituary, Google Books
- Scottish Architects
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