Purpose: To evaluate the long-term efficacy of anterior chamber iris-fixated phakic intraocular lens (PIOL) implantation in the treatment of high myopic (> -9.00 diopters [D]) or hyperopic (> +6.00 D) anisometropia in children with intolerance to spectacles or contact lenses. Methods: A total of 58 children with anisometropic myopia (range: -9.25 to-18.50 diopters [D]) and 13 children with anisometropic hyperopia (range: +6.00 to +8.50 D) underwent unilateral iris-claw PIOL implantation from 2008 to 2018. The mean age was 6.7 years. The mean follow-up was 38.5 months. Target refraction was emmetropia. Results: The cycloplegic refraction (mean spherical equivalent) improved from -12.47 D (range:-9.25 to-18.50 D) to -0.73 D (range: +0.75 to -1.50 D) in myopic eyes and reduced from +7.15 D (range: +6.00 to +8.50 D) to +0.94 D (range: -0.50 to + 1.75 D) in hyperopic eyes. Eighty-four percent of eyes were corrected to within +/- 1.00 D of emmetropia. The mean uncorrected distance visual acuity (UDVA) improved from 1.74 +/- 0.36 to 0.45 +/- 0.28 logarithm of the minimum angle of resolution (logMAR) (P = .0014). The mean corrected distance visual acuity (CDVA) changed from 0.68 +/- 0.32 to 0.27 +/- 0.15 logMAR (P = .02179). The safety index was 2.18 and the efficacy index was 1.51. The mean preoperative endothelial cell count of 2,874.7 cells/mm(2) changed to 2,685.3 cells/mm(2) at 2 to 6 years postoperatively. Binocular vision quality was improved in 55 patients. No patient had serious complications or lost any Snellen lines of CDVA. Conclusions: Iris-fixated PIOL implantation is an effective and safe method in the treatment of high anisometropic myopia and hyperopia and amblyopia in pediatric patients who are noncompliant with spectacles or contact lenses.