We investigated the efficacy and adverse effects of aminophylline and caffeine citrate in 180 premature neonates for 10 days and nights. Aminophylline (n = 98) and caffeine citrate (n = 82) were equally effective in preventing apnea and bradycardia. The caffeine citrate group had a lower median heart rate on day 3, fewer neonates with tachycardia and a smaller amount of gastric aspirate on day 7. The need for mononasal continuous positive airway pressure and respirator therapy was similar in both groups. We conclude that caffeine citrate is the drug of choice for apnea and bradycardia prophylaxis in premature neonates with a gestational age < or = 33 full weeks.