Head coach Justin Burnell got the perfect start from his first league game in charge as the South Yorkshire club also scored their first try-scoring bonus point since October and took a significant step towards ruling out the risk of relegation.
Clearly confident after their B&I Cup win over Ealing, Rotherham started brightly and had secured two converted tries via Lloyd Hayes and Calladine’s first before the 11th minute.
Bedford had opened the scoring with a Jake Sharp penalty and he converted when Sharp’s smart chip was gathered by winger Dean Adamson.
Calladine benefitted again after a driving maul as Rotherham went in 19-10 ahead and Toby Salmon broke off another maul early in the second period to claim that bonus point.
Will Goodwin improved again and converted his own solo try as the hosts unpicked Bedford yet again for a 33-10 lead.
Bedford hit back with a swift double blast from Michael Le Bourgeois and Dean Adamson, each converted.
Goodwin slotted two penalties, however, to end any fears of suffering a collapse, Bedford’s Miles Howard getting their final bonus point try.
Rotherham, meanwhile, head to London Welsh on Saturday.
Rotherham Titans: Scanlon, Keating, 1Davies (Jones 68), Owen, Hayes; Goodwin, Carter (A Davies 54); Hislop (Williams 60), Maddison (Edgson 73), Tampin (Thiede 66), Holmes (Preece 60), Salmon, Argyle, Calladine, Ryan (Maddison 40).
Bedford Blues: S Jones; Tapley, Le Bourgeois, Dodge (Staff 60), Adamson; Sharp (Dorrian 61), Burns; Lundberg (Parilli-Ocampo 46), James (Clare 46), Boulton, Latta (Blanchet 46), Wells (Howard 46), Tupai, Buggea, Conlon. Unused replacement: White.