To compare the difference between primary homoeopathic and conventional paediatric care in treating acute illnesses in children in their first 24 months of life. One hundred eight Indian singleton newborns delivered at 37 to 42 weeks gestation were randomised at birth (1:1) to receive either homoeopathic or conventional primary care for any acute illness over the study period. In the homoeopathic group, conventional medical treatment was added when medically indicated. Clinicians and parents were unblinded. Children in the homoeopathic group experienced significantly fewer sick days than those in the conventional group (RR: 0.37, 95% CI: 0.24–0.58; p < 0.001), with correspondingly fewer sickness episodes (RR: 0.53, 95% CI: 0.32–0.87; p = .013), as well as fewer respiratory illnesses over the 24-month period. They were taller (F (1, 97) = 8.92, p = .004, partial eta squared = 0.84) but not heavier than their conventionally treated counterparts. They required fewer antibiotics, and their treatment cost was lower. Conclusion: Homoeopathy, using conventional medicine as a safety backdrop, was more effective than conventional treatment in preventing sick days, sickness episodes, and respiratory illnesses in the first 24 months of life. It necessitated fewer antibiotics and its overall cost was lower. This study supports homoeopathy, using conventional medicine as a safety backdrop, as a safe and cost-effective primary care modality during the first 2 years of life.