Background: Many parents seek osteopathic care for their infants with colic. Our aim was to test the effectiveness of usual light touch osteopathic treatment on crying time for infants with ‘colic’. Methods: A superiority, two arm, single blinded (parent) multi-centre (UK, Australia and Switzerland), randomised controlled trial, included healthy infants between 1 and 69 days of age who excessively cried, fussed, or were distressed and difficult to console. The Test intervention consisted of usual light touch osteopathic treatment, the Control intervention simple light touch to random body locations with no treatment intent. Both groups received best practice advice and guidance. The primary outcome was the daily crying time, reported hourly by parents in a diary, for two-weeks. Secondary outcomes were parenting confidence, global change, satisfaction, and experience of care. Results: Sixty-six infants were recruited (32 Test: 34 Control group). Mean average daily crying time in the Test group was 124 min (SD = 69, n = 26) and in the Control 115 min (SD = 49, n = 29). After adjustment, infants in the Test group cried 2.2 min more per day than those in the Control group (CI95 % 􀀀 20 to 25 min, p = 0.849). Parents’ perceptions of global change in symptoms, satisfaction with, and experience of care were high and similar in both groups. There were no serious adverse events related to the treatments or the trial. Conclusion: Usual light touch osteopathic treatment was not superior to simple light touch without treatment intent. The biomechanical explanatory models and underpinning assumptions about the mechanisms of osteopathic intentional light touch care may require reconsideration. Trial registration: ACTRN12620000047998 (January 22, 2020).