Despite strong commitments of the central and provincial veterinary authorities in Vietnam to control highly pathogenic avian influenza H5N1 (HPAI-H5N1) in poultry and to diminish the risk of human infection, outbreaks continue to occur in poultry. This study describes the spatio-temporal distribution of HPAI-H5N1 outbreaks in Vietnam for the period December 2014-April 2018 using the space-time K-function and the space-time scan statistic. The space-time K-function analyses showed statistically significant spatio-temporal clustering of HPAI-H5N1 outbreaks in poultry during the study period of up to 50 days and 60 kilometres. The space-time scan statistic test identified three statistically significant space-time clusters of HPAI-H5N1 in the south of the country where the incidence of HPAI-H5N1 outbreaks was greater than that expected if outbreaks were randomly distributed in space and time. The analyses indicated shortfalls in the effectiveness of control measures used to control HPAI-H5N1 throughout the study period. Development of a better understanding of the relative impact of HPAI-H5N1 control measures (depopulation of infected flocks, vaccination, movement restrictions) on space-time interaction would allow animal health authorities to focus their efforts on control measures shown to have the greatest relative effect.