A recent epidemiological study systematically screened 250 prescription medications for associations with oesophageal cancer risk, using Scottish data, and identified an increased risk with use of prednisolone and warfarin. We investigated whether oral prednisolone or warfarin use was associated with increased oesophageal cancer risk. A case-control study was conducted within the Clinical Practice Research Datalink. In the primary analysis oesophageal cancer cases were identified from linked cancer registry records. Up to 5 cancer-free controls were matched to each case (based upon sex, birth year, GP practice and year of GP registration). Prednisolone and warfarin medications were identified from prescribing records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression after adjusting for covariates including demographics, comorbidities and medication use. There were 4552 oesophageal cancer cases and 22,601 matched control participants. Overall, there was no evidence of an increased risk of oesophageal cancer with oral prednisolone use (unadjusted OR=1.16 95% CI 1.06, 1.27 and adjusted OR=0.99 95% CI 0.89, 1.11) or warfarin use (unadjusted OR=1.12 95% CI 0.99, 1.28 and adjusted OR=1.08 95% CI 0.92, 1.27). In this large population-based study, oral prednisolone and warfarin were not associated with oesophageal cancer risk.