PURPOSE: Comparison of the efficacy of tropicamide eyedrops to the combination of 0.5% tropicamide and 5% phenylephrine eyedrops in order to achieve a proper dilation in premature infants undergoing screening for retinopathy of prematurity. METHODS: A prospective, randomized, double-blind study was conducted to compare the efficacy of two mydriatic regimens: one regimen consisting of three drops of 0.5% tropicamide (TTT regimen), the other regimen consisting of one drop of 5% phenylephrine and two drops of 0.5% tropicamide (PTT regimen). Thirty premature infants were enrolled and received both mydriatic regimens: one regimen in each eye. Outcomes were pupil dilation evaluated by the percentage of pupil diameter over cornea diameter, the percentage of pupil surface over cornea surface and the quality of the eye fundus examination. RESULTS: The percentage of pupil diameter over cornea diameter was 47.3% (±8.7) with the TTT regimen and 65.9% (±8.8) with the PTT regimen (p < 0.0001). The percentage of pupil surface over cornea surface was 23.1% (±8.3) with the TTT regimen and 43.8% (±7.3) with the PTT regimen (p < 0.0001). Thus, the pupil surface area was 1.9 times greater with the PTT than with the TTT regimen. Visualization of the retinal periphery was possible for 30 of 30 eyes dilated with the PTT regimen and for 16 of 30 eyes dilated with the TTT regimen (p < 0.0001). CONCLUSION: The dilated pupil surface area for the combination of 5% phenylephrine and 0.5% tropicamide was almost twice that for 0.5% tropicamide eyedrops alone and provided significantly superior quality of the eye fundus examination.