Traditionally, health ministries implement mass drug administration programmes for each neglected tropical disease (NTD) in separate and distinct campaigns. Many NTDs have overlapping endemicity suggesting co-administration might improve programme reach and efficiency, helping accelerate progress towards 2030 targets. Safety data are required to support a recommendation to undertake co-administration. For my PhD thesis, I sought to establish the safety profile and assess the community acceptance of a three-agent MDA combining albendazole (Alb), azithromycin, and ivermectin (Ivm) in comparison to the standard MDA regimen which separates the administration of azithromycin from the co-administered ivermectin and albendazole by a period of two weeks. I first conducted a literature review aimed at compiling and summarizing existing data on co-administration of ivermectin, albendazole and azithromycin, including both data on pharmacokinetic interactions and data from previous experimental and observationalstudies conducted in NTD-endemic populations. The results of the literature review showed that there was relatively limited data on the safety profile of co-administering these three drugs but that the available evidence suggested such a strategy is safe with an absence of clinically important drug-drug interactions, no serious adverse events reported and little evidence for an increase in mild adverse events. I then lead an open-label, non-inferiority cluster-randomized trial comparing the frequency of adverse events in communities receiving the co-administered ivermectin, albendazole and azithromycin to that in communities given albendazole and ivermectin MDA followed by azithromycin MDA after a two-week interval. The study took place in 58 gares (small administrative units) across two kebeles (sub-districts) in Kofele woreda (district) in the Oromia region of Ethiopia from November 2022 to January 2023. We randomly assigned 29 gares to the combined treatment arm and 29 gares to the control arm. The qualitative study I conducted was nested within the safety trial. Using semi-structured question guides, we conducted 16 key informant interviews (KII) with selected individuals involved in implementing MDA within the participating district. These individuals included health care providers and health department staff members, local government leaders, traditional governance leaders, religious leaders and elders. To better understand the perceptions of recipient communities, we also conducted four focus group discussions with key representational groups: male adults, female adults, female youths and male youths. The results of the trial showed that co-administration arm was non-inferior to the control Arm. The combined MDA arm consisted of 7292 individuals who were eligible to participate, of whom 7,068 received all three medications. The separate MDA arm consisted of 6219 eligible individuals of whom 6,211 received ivermectin and albendazole and 4,611 received azithromycin two weeks later. Overall, adverse events were reported by 197 (1.2%) of individuals. The most commonly reported adverse events included headache, gastrointestinal disturbance and dizziness. There were no serious adverse events in either arm. The results from the nested qualitative study showed that while there were some misgivings amongst community beneficiaries surrounding pill burden and refusals, the majority of participants appreciated the time and effort saved via the co-administered MDA strategy and preferred it to the standard, stand-alone MDAs.