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Abstract Background In November 2009, Sierra Leone conducted a preventive yellow fever (YF) vaccination campaign targeting individuals aged nine months and older in six health districts. The campaign was integrated with a measles follow-up campaign throughout the country targeting children aged 9–59 months. For both campaigns, the operational objective was to reach 95% of the target population. During the campaign, we used clustered lot quality assurance sampling (C-LQAS) to identify areas of low coverage to recommend timely mop-up actions. Methods We divided the country in 20 non-overlapping lots. Twelve lots were targeted by both vaccinations, while eight only by measles. In each lot, five clusters of ten eligible individuals were selected for each vaccine. The upper threshold (UT) was set at 90% and the lower threshold (LT) at 75%. A lot was rejected for low vaccination coverage if more than 7 unvaccinated individuals (not presenting vaccination card) were found. After the campaign, we plotted the C-LQAS results against the post-campaign coverage estimations to assess if early interventions were successful enough to increase coverage in the lots that were at the level of rejection before the end of the campaign. Results During the last two days of campaign, based on card-confirmed vaccination status, five lots out of 20 (25.0%) failed for having low measles vaccination coverage and three lots out of 12 (25.0%) for low YF coverage. In one district, estimated post-campaign vaccination coverage for both vaccines was still not significantly above the minimum acceptable level (LT = 75%) even after vaccination mop-up activities. Conclusion C-LQAS during the vaccination campaign was informative to identify areas requiring mop-up activities to reach the coverage target prior to leaving the region. The only district where mop-up activities seemed to be unsuccessful might have had logistical difficulties that should be further investigated and resolved.