BACKGROUND: The objective of this study was to investigate neurological short-term effects of craniosacral therapy as an ideal form of osteopathic manipulative treatment (OMT) due to the soft kinaesthetic stimulation. METHODS: Included were 30 preterm infants, with a gestational age between 25 and 33 weeks, who were admitted to the neonatal intensive care unit of the University Hospital of Graz, Austria. The infants were randomized either into the intervention group (IG) which received standardised craniosacral therapy, or the control group (CG) which received standard care. To guarantee that only preterm infants with subsequent normal neurodevelopment were included, follow up was done regularly at the corrected age (= actual age in weeks minus weeks premature) of 12 and 24 months. After 2 years 5 infants had to be excluded (IG; n = 12; CG: n = 13). General Movements (GMs) are part of the spontaneous movement repertoire and are present from early fetal life onwards until the end of the first half year of life. To evaluate the immediate result of such an intervention, we selected the General Movement Assessment (GMA) as an appropriate tool. Besides the global GMA (primary outcome) we used as detailed GMA, the General Movement Optimality Score (GMOS- secondary outcome), based on Prechtl’s optimality concept. To analyse GMOS (secondary outcome) a linear mixed model with fixed effects for session, time point (time point refers to the comparisons of the measurements before vs. after each session) and intervention (IG vs. CG), random effect for individual children and a first order autoregressive covariance structure was used for calculation of significant differences between groups and interactions. Following interaction terms were included in the model: session*time point, session*intervention, time point*intervention and session*time point*intervention. Exploratory post hoc analyses (interaction: session*time point*intervention) were performed to determine group differences for all twelve measurement (before and after all 6 sessions) separately. RESULTS: Between groups no difference in the global GMA (primary outcome) could be observed. The GMOS (secondary outcome) did not change from session to session (main effect session: p = 0.262) in the IG or the CG. Furthermore no differences between IG and CG (main effect group: p = 0.361) and no interaction of time*session could be observed (p = 0.658). Post hoc analysis showed a trend toward higher values before (p = 0.085) and after (p = 0.075) the first session in CG compared to IG. At all other time points GMOS were not significantly different between groups. CONCLUSION: We were able to indicate that a group of “healthy” preterm infants undergoing an intervention with craniosacral therapy (IG) showed no significant changes in GMs compared to preterm infants without intervention (CG). In view of the fact that the global GMA (primary outcome) showed no difference between groups and the GMOS (detailed GMA-secondary outcome) did not deteriorate in the IG, craniosacral therapy seems to be safe in preterm infants. TRIAL REGISTRATION: German Clinical Trials Register DRKS00004258 .