Aim and background: There is a lack of comprehensive and recent data on rhesus (Rh)-negative pregnancies in India. The aim of this study is to examine the demographics, isoimmunization status, usage of prophylactic treatment, and complications associated with Rh-negative pregnancies in India. Materials and methods: This is an interim analysis of an ongoing real-world observational study targeting the recruitment of 20,000 Rh-negative pregnant women throughout India. This article presents data from 1,421 participants who were followed prospectively for 3 months. Participants’ demographics, obstetrics history, usage of prophylactic treatment, and pregnancy-related complications were recorded. Data were analyzed using descriptive statistics for all the outcome variables. Results: The maximum number of participants belonged to the West region (47.4%). The mean gestational age of the participants was 37.7 weeks. There was an equal representation of primigravida and multigravida participants in the study population. The available indirect Coombs test data showed that most of the participants (116 of 125) were negative for circulating antiglobulin in the current pregnancy. However, isoimmunization during the current pregnancy occurred in 9 participants (9 of 125; 7.2%). Overall, 25.7% of the participants received anti-D prophylaxis during their current pregnancy. Conclusion: This real-world evidence study demonstrates that most Rh-negative women carrying Rh-positive fetus are at risk of becoming sensitized to the Rh antigen. Despite the availability of prophylactic treatment, there are women who are getting sensitized. Hence, there is a need to create awareness among the Indian population about the Rh-disease-associated risks and available preventive measures to reduce the mortality rates. Clinical significance: Anti-D prophylaxis is the most effective method to prevent sensitization in Rh-negative pregnant women. Anti-Rh (O) D immunoglobulin is a must administered drug both in antenatal and postnatal phases of pregnancy to prevent Rh-negative pregnant women from getting sensitized. Thus, further reducing the burden of Rh-sensitization in India and having healthy motherhood.