By December 2007, there was a continuum of Highly Pathogenic Avian Influenza (HPAI) H5N1 affected countries along the West African coast from Cote d’Ivoire to Cameroon. In all, 8 countries in West Africa had recorded HPAI H5N1 (Niger, Burkina Faso, Cote D’Ivoire, Ghana, Togo, Benin, Nigeria, and Cameroon). There is concern about the danger posed by circulation of the virus as these countries are members of ECOWAS and there is constant movement of people and goods and trade between them. At a workshop in Accra in November 2008, participants identified re-introduction of the virus into Ghana as a major challenge. The risk question posed was “What is the risk of re-introduction of HPAI H5N1 virus from neighbouring countries (Burkina Faso, Cote d’Ivoire and Togo) into Ghana via cross-border trade and movements involving live birds, poultry products and fomites?“. Three release risk pathways involving Cote d’Ivoire, Burkina Faso and Togo were developed. A questionnaire was developed to elicit responses from identified experts to provide information. Credible information was received from Cote d’Ivoire and Burkina Faso. There was no response from Togo. A qualitative risk assessment following the OIE framework was undertaken to address the risk question. The qualitative risk estimates for the release pathways ranged from negligible to very low with high uncertainty. During outbreaks in neighbouring countries when birds are infected, the risks will vary and are likely to be higher. The highest risk of re-introduction of HPAI H5N1 virus to Ghana is the pathway involving cross-border trade and movement of poultry, poultry products, people and fomites from Cote d’Ivoire with risk estimates being negligible to medium. This is because poultry and poultry products are illegally sent into Ghana (despite a ban on poultry and poultry products) and the existence of farms along the border in the two countries under similar management and therefore sharing facilities. The steps of the pathway for the re-introduction from Cote d’Ivoire to Ghana associated with higher risks included the probabilities of introduction of live birds, eggs and egg trays, and day-old chicks and the probabilities of contamination of traders and poultry workers on small farms. From Burkina Faso, the steps with higher risks posing a threat for re-introduction of HPAI to Ghana included the probabilities of introduction of live household birds; the probability of transporting guinea fowl eggs; the probabilities of contamination and transporting of baskets used for live birds and egg containers; the probability of traders using vehicles to markets and the probability of maize being imported for use as poultry feed. From Togo, the steps with higher risks posing a threat for reintroduction of HPAI to Ghana included the probability of introduction of live household birds; the probability of contamination of poultry workers and the probability of importing frozen turkey tails and carcasses. These could be targeted as preventive or critical mitigation points. The high level of uncertainty associated with most of the risk estimates point to significant gaps in knowledge of the epidemiology of HPAI and/or poultry production or trade in West Africa. Therefore the risk estimates have to be interpreted with extreme caution. There is the need for targeted data collection to fill some of the relevant knowledge gaps. The particular areas are the prevalence of HPAI in household birds and wild and scavenging birds, and movement patterns of people and poultry and poultry products across the borders.