This article traces the twentieth-century ‘afterlife’ of Indian opium, following the global trajectories of the commodity beyond the decades of prohibition, when its international trade was broadly viewed as being in terminal decline. The article demonstrates how opium from Malwa, Bengal and Bihar was brought into the ambit of Western pharmaceuticals during the two World Wars. In spite of the scepticism of temperance-minded nationalists, it foregrounds the crop’s regular integration into these commodity chains in the early decades of Indian independence and its ascent as the key raw material in the USA’s expanding painkiller market. Yet this putative success, this article suggests, was temporary, and Indian opium would fuel a burgeoning domestic narcotics crisis, before being felled, again, by pharmacological, botanical and geopolitical transformations at the century’s end. In offering a history of Indian opium which stretches beyond the traditional ending point offered by prohibition, this article locates opium within a broader connective history of Indian commodities, demonstrating how one particularly electric commodity was integrated within a widening purview of Western economic power, and American pharmaceutical hegemony in particular.