BACKGROUND: The topical administration of eyedrops is often an unpleasant procedure in the pediatric population. We sought to learn whether a combination mydriatic-cycloplegic solution would be an effective cycloplegic if delivered as a spray. METHODS: We conducted a prospective, examiner-masked, parallel-group study and randomized 38 subjects (age range 6 months to 12 years, mean = 7.3 years) into four groups such that the same combination mydriatic-cycloplegic solution was administered under the following conditions: 1) eyedrops to eyes that were open; 2) eyedrops to eyes that were closed; 3) spray to eyes that were open; 4) spray to eyes that were closed. Both eyes of each subject received the solutions administered under one of the four conditions. Residual accommodation was measured using dynamic retinoscopy and the subjective push-up method, where applicable, at times 0, 10, 20, 30, 45, and 60 mins following administration of the medications. RESULTS: Repeated measures analysis of covariance revealed no statistically significant difference (p > 0.05) in cycloplegic efficacy among the four methods of drug delivery. CONCLUSIONS: The results of this study suggest that administering cycloplegics by spray to the closed eye is as efficacious as instilling eyedrops to the open eye. Use of a cycloplegic spray can have important clinical advantages compared to conventional cycloplegic eyedrops administered to children.