This study investigated the degree of risk of handicap in twins, triplets, quadruplets and quintuplets and associated factors, and examined the clustering tendency of handicaps. The sample was recruited from the Kinki University Twin and Higher Order Multiple Birth Registry. This panel consisted of 705 pairs of twins (1410 twins), 96 sets of triplets (287 triplets excluding 1 infant death), 7 sets of quadruplets (27 quadruplets excluding 1 infant death), and 2 sets of quintuplets (10 quintuplets), all of whom were born after 1977. The incidence of handicap was 3.7% in twins, 8.7% in triplets, 11.1% in quadruplets, and 10.0% in quintuplets. The risk of prodicing at least 1 handicapped child was approximately 1 in 13 pairs of twins (7.4%), 1 in 4 or 5 sets of triplets (21.6%), and 1 in 2 sets of quadruplet and quintuplets (50%). There was a significantly higher clustering tendency of handicaps in twins and triplets compared with the expected frequency calculated from the incidence rate of handicap. Four significant risk factors for subsequent handicap were found by logistic regression: gestation number, shortening of gestational age, premature rupture of the membrane, and toxemia during pregnancy.