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Background The AVENIR cluster-randomised trial evaluated whether biannual mass drug administration (MDA) of azithromycin improved childhood mortality among infants in Niger, a high-mortality, high-malnutrition setting.Methods Weight-for-age z-score (WAZ) was a prespecified secondary outcome of the trial. In this analysis, 2880 communities in the Dosso and Tahoua regions and 51 687 infants with two sequential weight measurements were included. Weight was assessed at baseline and 6 months post treatment, and WAZ was calculated using WHO standards. To include two subsequent measures of WAZ, infants at baseline were 1–5 months old. Linear mixed-effects models compared mean WAZ between azithromycin and placebo arms, with additional analyses examining community-level means, categorical underweight outcomes and predefined subgroups.Results At follow-up, mean WAZ was −1.39 in the azithromycin arm and −1.38 in the placebo arm, with no detectable difference (mean difference 0.00, 95% CI −0.05 to 0.04, p=0.94). Odds of moderate-to-severe or severe underweight also did not differ between groups. Subgroup analyses by baseline nutritional status, age, sex, community size and distance to health centres showed consistent null effects, though a small, non-significant improvement in WAZ was observed in infants treated during the rainy season compared with the dry season.Conclusion These findings align with prior large-scale trials that demonstrated mortality benefits but no sustained effects of azithromycin on growth. Taken together, the results suggest that while azithromycin MDA reduces childhood mortality, it is unlikely to provide medium-term improvements in weight gain, highlighting the need for complementary nutritional interventions to address undernutrition in similar settings.