Background: Micronutrient deficiencies are widespread in India. Soil-transmitted helminth (STH) infections are acquired by interaction with soil and water contaminated by human feces and lead to blood loss and poor micronutrient absorption. The current recommendation for control of STH-related morbidity is targeted deworming, yet little is known about the effectiveness of deworming on micronutrient status in varying sanitation contexts. Ranging between 1% and 40% prevalence across Indian states, open defecation (OD) remains high despite India's investments at elimination by promoting community-wide sanitation. This variation provides an opportunity to study the relationship between deworming, micronutrient status, and OD at-scale. Methods and findings: Cross-sectional datasets that were representative for India were obtained the Comprehensive National Nutrition Survey in 2016 to 2018 (n = 105,060 individuals aged 1 to 19 years). Consumption of deworming medication was described by age and community OD level. Logistic regression models were used to examine the relationship between deworming, cluster OD, and their interactions, with anemia and micronutrient deficiencies (iron, zinc, vitamin A, folate, and vitamin B12), controlling for age, sex, wealth, diet, and seasonality. These regression models further allowed us to identify a minimum OD rate after which deworming becomes ineffective. In sensitivity analyses, the association between deworming and deficiencies were tested in subsamples of communities classified into 3 OD levels based on statistical tertiles: OD free (0% of households in the community practicing OD), moderate OD (>0% and <30%), or high OD (at least 30%). Average deworming coverage and OD prevalence in the sample were 43.4% [IQR 26.0, 59.0] and 19.1% [IQR 0, 28.5], respectively. Controlling for other determinants of nutritional status, adolescents living in communities with higher OD levels had lower coverage of deworming and higher prevalence of anemia, zinc, vitamin A, and B12 deficiencies. Compared to those who were not dewormed, dewormed children and adolescents had lower odds of anemia (adjusted odds ratio 0.72, (95% CI [0.67, 0.78], p < 0.001) and deficiencies of iron 0.78, (95% CI [0.74, 0.82], p < 0.001) and folate 0.69, (95% CI [0.64,0.74], p<0.001)) in OD free communities. These protective effects remained significant for anemia but diminished for other micronutrient deficiencies in communities with moderate or high OD. Analysis of community OD indicated a threshold range of 30% to 60%, above which targeted deworming was no longer significantly associated with lower anemia, iron, and folate deficiency. The primary limitations of the study included potential for omitted variables bias and inability to capture longitudinal effects. Conclusions: Moderate to high rates of OD significantly modify the association between deworming and micronutrient status in India. Public health policy could involve sequencing interventions, with focus on improving deworming coverage in communities that have achieved minimum thresholds of OD and re- triggering sanitation interventions in high OD communities prior to deworming days, ensuring high coverage for both. The efficacy of micronutrient supplementation as a complementary strategy to improve nutritional outcomes alongside deworming and OD elimination in this age group needs further study. Using data from India, Chakrabarti and colleagues evaluate whether higher open defecation levels diminished the protection provided by deworming against anaemia or micronutrient deficiencies. Author summary: Why was this study done?: Deworming is recommended to tackle soil-transmitted worm infections in low- and middle-income countries (LMICs), but the effectiveness of deworming provided on a large scale varies significantly. Sanitation levels across communities are likely to influence the impact of deworming in populations due to high rates of reinfection, but no studies have investigated these links. Despite well-intended programs intended to eliminate open defecation in India, this behavior persists in certain communities. This study was done to test whether higher open defecation levels diminished the protection provided by deworming against anemia or micronutrient deficiencies among Indian children and adolescents. What did the researchers do and find?: We used a cross-sectional dataset (sample size 105,060 individuals) representative of Indian children and adolescents to look at links between open defecation, deworming, anemia, and micronutrient deficiencies. We found that deworming coverage remains low in India, especially among young children and adolescents out of school, indicating the need for enhanced and expanded deworming interventions. After accounting for the influence of age, sex, wealth, education, diet, and season, dewormed children in areas without open defecation had lower rates of anemia (28% lower), iron deficiency (22% lower), and folate deficiency (31% lower); however, in communities with open defecation, dewormed children showed similar deficiency levels as those not dewormed. What do these findings mean?: Our findings suggest that open defecation diminishes the protection provided by deworming medication against anemia and micronutrient deficiencies in India. The findings highlight the importance of sequencing sanitation interventions such as behavior change campaigns before deworming initiatives in high open defecation communities. This study cannot establish causation because the statistical models were based on observing associations at a single point in time rather than tracking changes over time. [ABSTRACT FROM AUTHOR]