Mass azithromycin distribution reduces child mortality in some settings, potentially through reductions in nasopharyngeal carriage of Streptococcus pneumoniae, but has been associated with increased antimicrobial resistance. Individual-level data are lacking on the impact of azithromycin on antimicrobial resistance over time. We analyzed data from a double-blind, randomized placebo-controlled trial (ClinicalTrials.gov; NCT02414399) which followed 1,398 hospitalized Kenyan children to evaluate the impact of a 5-day course of oral azithromycin at discharge from hospital on pneumococcal carriage and the proportion of isolates (among a random sample) resistant to azithromycin. Randomization to azithromycin or placebo (1:1) was stratified by enrollment county (Kisii or Homa Bay). Using generalized estimating equations, we calculated prevalence ratios (PRs) and 95% confidence intervals for the intervention, adjusting for enrollment site. Overall, 1,253/1398 (89.6%) enrolled children received antibiotics during their hospitalization. Pneumococcal carriage at discharge was similar among children randomized to the azithromycin group (158/702 [22.5%]) compared to the placebo group (171/696 [24.6%]; p = 0.4) and did not differ at month 3 (65.6% vs 67.0%; PR:0.98[0.90, 1.06]) or month 6 (66.7% vs 66.5%; PR:1.00[0.92, 1.08]). At discharge, 15.7% of isolates were resistant to azithromycin and there was no difference between azithromycin-treated and placebo groups at month 3 (35/266 [13.2%] vs 32/256 [12.5%]; PR:1.06[0.86, 1.66]) or month 6 (41/245 [16.7%] vs 43/243 [17.6%]; PR:1.01[0.69,1.49]). Azithromycin treatment did not effect pneumococcal carriage or antimicrobial resistance 3- or 6-months post-randomization. High inpatient antibiotic use in this recently discharged population may have reduced any further impact of azithromycin.