Introduction: In Germany in recent years, a growing number of parents are seeking help from osteopaths for the perceived health complaints of their infants and children. However, reliable evidence for the effectiveness of osteopathic interventions for this group of patients is largely lacking. Objective: To observe and document changes in the symptoms of certain health disturbances, as perceived by parents, during the course of an osteopathic treatment of their baby, and associated side effects. Methods: A single-arm, prospective, multicenter, observational study was chosen as the study design. Parents who contacted an osteopathic practice with any of the following 5 health disturbances were invited to include their baby into the study: idiopathic infant asymmetry (IA), deformational plagiocephaly (DP), feeding disorders (FD), excessive crying (EC), and sleep disorders (SD). Osteopaths performed osteopathic treatment as usual for these conditions, and the parents were asked to rate the perceived severity of symptoms on standardized forms including numerical rating scales (NRS 0–10). In DP, the head circumference of the child’s skull was measured with a craniometer, and the cranial vault index (CVAI) was calculated. Results: 230 osteopaths agreed to participate, 151 osteopaths returned parental ratings. 1,136 infants were treated 2.8 ± 1.1 times (mean ± SD). IA was the most prevalent disturbance (48%), followed by EC (18%), FD (15%), DP (14%), and SD (4%). In IA, perceived asymmetry as rated on the NRS improved from 6.1 to 1.1, a mean improvement of 82%. In DP, the CVAI improved from 8.0 to 4.0%, a mean improvement of 51%. FD improved by 77%, EC by 70% (from 7.7 to 2.3 on the NRS) and SD by 56%. Adverse reactions with a timely association with osteopathic treatments were reported in 3.5% of all treatments, probably reflecting typical day-to-day variations in symptoms. In a total of 3,212 treatments, there was not a single serious adverse reaction affecting infant health. Conclusions: This is one of the largest studies worldwide to date on the osteopathic treatment of infants. Osteopathic treatment was associated with major positive changes in the severity of perceived health complaints as assessed by parents, which in most cases were resolved as a matter of concern, and was proved to be a safe treatment modality among a large number of therapists. Based on these results, confirmatory intervention studies can and should be planned and conducted.