Positional plagiocephaly (PP) denotes flattening of the skull that occurs frequently in healthy infants. Aim of this study was to estimate the prevalence of positional plagiocephaly and to identify the risk factors in a cohort of healthy infants in order to help prevention of PP. In a prospective design, all healthy full-term infants, ranging from 8 to 12 weeks of age, who presented at the public immunization clinic in Ferrara, were eligible for the study. After obtaining informed consent, we interviewed the parents and examined the infants using the Argenta’s assessment tool. Of 283 infants examined, 107 (37.8%) were found to have PP at 8–12 weeks of age. In 64.5%, PP was on the right side, 50.5% were male and 15% presented also with brachycephaly. Risk factors significantly associated were lower head circumference, advanced maternal age, Italian compared to African, and supine sleep position, in particular for infants born at 37 weeks, preference for one side of the head. In logistic regression, risk factors significantly associated were lower birth weight, advanced maternal age, and supine sleep position.