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Abstract Background The Zambian Ministry of Health implemented a reactive one-dose Oral Cholera Vaccine (OCV) campaign in April 2016 in three Lusaka compounds, followed by a pre-emptive second-round in December. Understanding uptake of this first-ever two-dose OCV campaign is critical to design effective OCV campaigns and for delivery of oral vaccines in the country and the region. Methods We conducted 12 Focus Group Discussions (FGDs) with men and women who self-reported taking no OCV doses and six with those self-reporting taking both doses. Simple descriptive analysis was conducted on socio-demographic and cholera-related data collected using a short questionnaire. We analyzed transcribed FGDs using the framework of dose, gender and geographic location. Results No differences were found by gender and location. All participants thought cholera to be severe and the reactive OCV campaign as relevant if efficacious. Most reported not receiving information on OCV side-effects and duration of protection. Those who took both doses listed more risk factors (including ‘wind’) and felt personally susceptible to cholera and protected by OCV. Some described OCV side-effects, mostly diarrhoea, vomiting and dizziness, as the expulsion of causative agents. Those who did not take OCV felt protected by their good personal hygiene practices or, thought of themselves and OCV as powerless against the multiple causes of cholera including poor living conditions, water, wind, and curse. Most of those who did not take OCV feared side-effects reported by others. Some interpreted side-effects as ‘western’ malevolence. Though > 80% discussants reported not knowing duration of protection, some who did not vaccinate, suggested that rather than rely on OCV which could lose potency, collective action should be taken to change the physical and economic environment to prevent cholera. Conclusions Due to incomplete information, individual decision-making was complex, rooted in theories of disease causation, perceived susceptibility, circulating narratives, colonial past, and observable outcomes of vaccination. To increase coverage, future OCV campaigns may benefit from better communication on eligibility and susceptibility, expected side effects, mechanism of action, and duration of protection. Governmental improvements in the physical and economic environment may increase confidence in OCV and other public health interventions among residents in Lusaka compounds.