Background: Since the turn of the 21 st century, ready-to-use foods have emerged as the preferred solution to the nutrient needs of specific target groups. This study assessed the efficacy of a peanut- based ready-to-use supplementary food (RUSF) on the nutritional status of women of reproductive age (WRA) in peri-urban settlements in the Ga East Municipality in the Greater-Accra region of Ghana. Methods: This was a randomized controlled trial among 134 WRA aged 15-49 years. Of the 80 women who completed the study, 47 (58.8%) were in the intervention group whilst 33 (41.2%) were in the control group. The intervention group received 330ml RUSF thrice weekly for 12 weeks whilst the control group received no food. Proximate composition of the RUSF was determined using standard procedures. Baseline background characteristics, dietary intake, anthropometric, haematological and biochemical indices were measured. At 6 and 12 weeks, all measurements were repeated except for dietary intake and background characteristics. Height, weight, neck circumference (NC) and hip circumference (HC) were measured with a stadiometer, digital weighing scale and tape measure respectively. Whole blood was used to determine full blood count using the haematology automated analyzer. Sickling was determined by blood staining. Serum ferritin and iron were measured by an automated immunoassay and by the colometric agar-based method. C-reactive protein (CRP) was determined using an enhanced turbidimetric immunoassay technique. Serum total proteins, albumin and globulins were measured by Biuret, Bromocresol green and glyoxylic acid methods. Changes in baseline and endline within and between groups were compared using paired and independent sample t-tests. Results: The mean age of the women was 29 ± 8 years. Based on dietary recall, 59.0%, 66.4%, 34.3%, 73.9% and 73.4% of the women met their recommended daily allowance (RDA) for total calories, protein, fats, iron and vitamin C respectively but none of the them met the RDA for folate. Nonetheless the data showed that 86.6% were food insecure. Eighty-three percent (83.0%) of the women were sickle cell negative. The energy, carbohydrate, protein, fat and ash content of the RUSF on dry matter basis were 564.52, 59.15, 22.93, 15.26 and 2.66g/100g respectively. Change in body mass index (BMI) in the intervention group was 0.96 ± 2.83 (p<0.05) whilst the control group was 0.42 ± 3.29 (p>0.05). Haemoglobin concentration in the intervention group increased from 12.26 ± 2.06g/dL to 12.43 ± 2.00g/dL and the control group decreased from 12.52 ± 1.76g/dL to 11.71 ± 1.33g/dL. Prevalence of anaemia was >30% in both groups. CRP was positive for less than 20% of the women. No differences in NC, HC, total proteins, albumin, globulins, iron and ferritin were observed between the two groups. Conclusions: Supplementation with RUSF for 12 weeks was associated with a modest increase in BMI and haemoglobin amongst the women who received the RUSF. The RUSF has the potential to help improve iron deficiency anaemia which is a public health concern in Ghana and most developing countries.