Retrospective analysis of the clinic database between 2003-2005 indicated that tetanus (27 cases), colic (134), rabies (7), strangles (17), hyena bite (429), dystocia (39), hernia (27) and car accidents are the major causes of direct mortality in donkeys of Central Ethiopia. The case fatality rates of donkeys affected by these diseases were: tetanus 22%, colic 27%, dystocia 15%, strangles 12%, hernia 11%, hyena bite 7% and rabies 100%, in clinical intervention sites of the Donkey Sanctuary. In the non-intervention areas the mortality rates are expected to be higher as there would be no treatment intervention. In this paper the two major causes of mortality: tetanus and colic are discussed. In the project in Ethiopia, treatments of advanced cases of tetanus following standard procedures have been successful. Of 27 cases treated 21 have been cured. The treatment has, however, been expensive, costing the project an average of 1400 Eth Birr per donkey (mature donkey costs 300-400 Eth Birr) and requiring a long period of hospitalisation. In an ideal situation, prophylactic immunisation is the best option. Economic realities however prohibit such an option from being feasible in countries like Ethiopia. An extension system and strategy that focus on the prevention of wounds using proper harnesses/saddles and institution of a sound hoof care programme is the option in mind. Colic characteristics are: gastric impaction 8%, obstruction of small intestines 7%, colonic impactions 19%, flatulent colic 23%, enterolithiasis/foreign bodies 24%, throboembolism due to strongylosis and undiagnosed cases 19%. Free access to mouldy or coarse feed, ingestion of polythene bags, fertiliser sacks and used fabrics of nylon clothes were the major causes. Common sites of lodgement for enteroliths were the proximal portion of the transverse colon, transverse and small colons. Enterolith/foreign body was often diagnosed in pregnant donkeys with colic. Few cases were relieved by surgery. A considerable number of the enteroliths were removed by manual traction. Veterinary intervention alone will do little to alleviate such problems. The use of school children to collect polyethylene bags and fertiliser sacks, improve farmers' awareness of the risk being posed by these materials and that of braided nylon ropes. Encouraging farmers to prevent donkeys from grazing at waste disposal sites is also another preventive measure that can be practised against colic. Extension and education programmes for owners should pay particular attention to these issues.