Although the optimal strategy for preventing contrast-induced acute kidney injury (CI-AKI) has not yet been established, the current strategy focuses on adequate periprocedural hydration, the use of a low amount of low or iso-osmolar contrast medium, and the application of adjunctive therapies, including hemofiltration, hemodialysis and drugs. Previous trials and meta-analyses concerning the use of the adenosine antagonist theophylline have revealed contradictory results. We sought to evaluate the effect of theophylline in CI-AKI prevention in well-hydrated elderly patients with chronic kidney disease. We therefore conducted a randomized, double-blind, placebo-controlled trial involving 56 patients who had been referred for cardiac coronary angiography and/or angioplasty. 31 of these patients were randomly assigned to 200 mg theophylline IV before the procedure, and 25 to a placebo. The iso-osmolar contrast medium iodixanol was used. The primary endpoint was an increase in serum creatinine at study termination 48 h after contrast medium administration. Baseline characteristics in the placebo and theophylline groups were similar in terms of median age (75 years), estimated glomerular filtration rate (33 ± 10 vs. 33 ± 10 ml/min/1.73 m²; p = 0.87), diabetes mellitus (80 vs. 71%; p = 0.54), and amount of contrast used (94 ± 35 vs. 95 ± 38 ml; p = 0.89). There was no difference in serum creatinine at baseline (2.06 ± 0.59 vs. 2.02 ± 0.45 mg/dl; p = 0.62) or study termination (2.06 ± 0.68 vs. 2.10 ± 0.53; p = 0.79). A prophylactic effect of theophylline was not observed. The incidence of renal impairment following exposure to the contrast medium was low. This fact can be attributed to adequate parenteral hydratation and the use of the minimum amount of contrast medium necessary.