OBJECTIVE To compare the efficacy of pupil dilation between a single dose and three doses of 1% tropicamide and 10% phenylephrine for binocular indirect ophthalmoscopy. METHODS A prospective randomized double-blind clinical controlled trial was conducted. All patients underwent the binocular indirect ophthalmoscopy and met the inclusion criteria were randomized into two groups using block randomization. Group A received a single dose of 1% tropicamide and 10% phenylephrine eye drops, and Group B received three doses of the same drugs. The primary outcome was the horizontal pupil diameter measured by slit-lamp biomicroscope (Haag-Streit model 900) before and at 10, 15, 20, 25 and 30 minutes after eye drop instillation. The clinical equivalence of the efficacy of pupil dilation between the two groups was defined as the difference of less than or equal to 1 mm (-1 mm to + 1 mm). RESULTS Eighty patients (160 eyes) were randomized into 40 patients (80 eyes) in group A and 40 patients (80 eyes) in group B. The mean pupil sizes at baseline of group A were 3.51 +/- 0.63 mm in the right eye and 3.39 +/- 0.67 mm in the left eye. Those in group B were 3.61 +/- 0.67 mm in the right eye and 3.66 +/- 0.72 mm in the left eye. The mean pupil diameters at 30 minutes of group A were 7.34 +/- 0.51 mm in the right eye and 7.41 +/- 0.56 mm in the left eye, whereas those of group B were 7.49 +/- 0.45 mm in the right eye and 7.51 +/- 0.40 mm in the left eye. The mean difference of the pupil size between the two groups was 0.15 mm (p = 0.175) in the right eye and 0.l0 mm (p = 0.362) in the left eye. The 95% confidence intervals of the difference in pupil size were -0.36 to 0.07 mm in the right eye and -0.32 to 0.12 mm in the left eye. CONCLUSIONS The 95% confidence interval of the difference in pupil size lay entirely within the range of equivalence. The single dose of 1% tropicamide and 10% phenylephrine was clinically equivalent to the three doses of the same drugs.