The purpose of this study was to clarify the characteristic child-rearing problems for mothers of multiple children who conceived after infertility treatment as compared to mothers of multiple children who conceived spontaneously. The subjects were 990 mothers of multiple children: 359 who conceived after infertility treatment and 631 who conceived spontaneously. Mothers who conceived after infertility treatment were more delighted when informed of a multiple pregnancy than those who conceived spontaneously. In addition, with respect to anxiety during twin pregnancies, mothers of twins who conceived after infertility treatment showed lower rates of anxiety about nursing the infants and economic concerns than those of twins who conceived spontaneously. However, after delivery, mothers who conceived after infertility treatment showed a higher rate of depressive symptoms than those who conceived spontaneously. After adjusting for each associated factor using logistic regression, the risk of depressive symptoms in mothers who conceived after infertility treatment was significantly associated with disabled multiple children and the methods for alleviating stress. The odds ratio indicated that mothers with at least one disabled child were twice as likely to have depressive symptoms as mothers with no disabled children. Furthermore, the odds ratio indicated that mothers who used no methods for alleviating stress were twice as likely to have depressive symptoms than those who did.