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. 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. 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/mm2 changed to 2,685.3 cells/mm2 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. Iris-fixated PIOL implantation is an effective and safe method in the treatment of high anisome-tropic myopia and hyperopia and amblyopia in pediatric patients who are noncompliant with spectacles or contact lenses. [J Pediatr Ophthalmol Strabismus. 2023;60(3):203-209.].