The goal of this study was to determine whether an instrument that uses referral criteria having a high specificity (plusoptiX S08) would fail to refer children who have significant amblyopia and who would have been detected by an instrument using refractive criteria that have a high referral rate and presumed higher sensitivity (SPOT). A total of 2801 cases were screened with SPOT: at an average age of 5.1 years (1.4 to 6.3). In all, 307 (11%) were referred by SPOT and then screened by plusoptiX. All were referred for formal eye examinations: 110 received this examination and 100 were of adequate quality. Forty-three cases had amblyopic risk factors. The positive predictive value of SPOT was 43% and 15% had amblyopia. Positive predictive value for the plusoptiX was 72.7% and 27% had amblyopia. Eleven referred by SPOT but not by plusoptiX had amblyopia risk factors or amblyopia and would have been missed by plusoptiX. Most referrals were for astigmatism and anisometropia. The authors conclude that the plusoptiX with modified refraction criteria can be used as a highly specific screening device.