BackgroundMalnutrition remains a health challenge for women aged 15 to 49 years and their infants. While Nutrition Assessment Counselling and Support (NACS) is considered a promising strategy, evidence on its effectiveness remains scanty. This study assessed the effect of comprehensive NACS package on the mother-infant practices, health and nutrition outcomes in two districts in Eastern Uganda.MethodsA comparative non equivalent quasi experimental design was employed with two groups; Comprehensive NACS (Tororo) and Routine NACS (Butaleja). Pregnant mothers were enrolled spanning various trimesters and followed through the antenatal periods and post-delivery for health and nutrition status. Infants were followed for feeding practices, health and nutritional status at birth and weeks 6, 10, 14 and at month 6, 9 and 12 post-delivery. Propensity score matching ensured study group comparability. The NACS effect was estimated by nearest neighbour matching and the logistic regression methods. Statistical analysis utilised STATA version 15 and R version 4.1.1.ResultsA total of 666/784 (85%) with complete data and were analysed (routine: 412, comprehensive: 254). Both groups were comparable by mothers’ age, MUAC, prior antenatal visits, meal frequency, micronutrient supplementation and instances of maternal headache, depression and diarrhoea. However, differences existed in gestation age, income, family size, education and other living conditions. Comprehensive NACS infants exhibited higher infant birth weights, weight- for- age z-scores at the 3rd-6thvisits (p<0.001), length- for- age z scores at the 4th-7thvisits (p<0.001) and weight-for-length z-scores at the 3rd- 5th(p<=0.001) visits. Despite fewer episodes of diarrhoea and fever, upper respiration infections were higher.ConclusionThe comprehensive NACS demonstrated improved mother-infant nutritional and other health outcomes suggesting the need for integrated and holistic care for better maternal, infant and child health.