PURPOSE: To compare the cost and effectiveness of three cycloplegic agents among Nigerian children. METHODS: Two hundred thirty-three children aged 4 to 15 years attending outpatient eye clinics in Nigeria were randomized to (1) 1% cyclopentolate, (2) 1% cyclopentolate and 0.5% tropicamide, or (3) 1% atropine drops in each eye (instilled at home over 3 days). Ten children were lost to follow-up, nine from the atropine group. An optometrist measured the residual accommodation (primary outcome), dilated pupil size, pupil response to light, and self-reported side effects (secondary outcomes). Caregivers were interviewed about costs incurred due to cycloplegia (primary outcome). The incremental cost effectiveness ratios (ICERs) were calculated as the difference in cost divided by the difference in effectiveness comparing two agents. The 95% confidence intervals (CI) for ICERs were estimated through bootstrapping. RESULTS: The atropine group had significantly lower mean residual accommodation (0.04 +/- 0.01 D [SE]), than the combined regimen (0.36 +/- 0.05 D) and cyclopentolate (0.63 +/- 0.06 D) groups (P < 0.001). Atropine and the combined regimen produced better results for negative response to light and dilated pupil size than cyclopentolate. Atropine was more expensive, but also more effective, than the other agents. The ICER comparing atropine to the combined regimen was 1.81 (95% CI = -6.31-15.35) and compared to cyclopentolate was 0.59 (95% CI = -3.47-5.47). The combined regimen was both more effective and less expensive than cyclopentolate alone. CONCLUSIONS: A combination of cyclopentolate and tropicamide should become the recommended agent for routine cycloplegic refraction in African children. The combined regimen was more effective than cyclopentolate, but not more expensive, and was preferable to atropine, since it incurred fewer losses to follow-up.