A region-wide population-based post-mass drug administration (MDA) coverage survey was conducted 3 weeks following the 2016 trachoma MDA in Amhara, Ethiopia. The prevalence of self-reported side effects was assessed among those who self-reported receiving azithromycin. A total of 16,773 individuals from 5,129 households reported taking azithromycin during the 2016 MDA in Amhara. The regional prevalence of any self-reported side effect was 9.6% (95% CI: 8.3-11.2%) and ranged from 3.9% to 12.4% among the 10 zones. The most common reported side effects were abdominal pain (53.1%), nausea (21.7%), vomiting (12.8%), and diarrhea (12.5%). Side-effect prevalence among female members was higher than in male members (11.6% versus 7.6%; P < 0.001) and increased with age. After an average of 8 years of annual MDA, the prevalence of self-reported side effects was less than 10% in this population.