Ethiopia has 7.1 million donkeys and mules, the majority of which are used as pack animals. Factors such as poor harness quality, long-distance traveling, and heavy cartloads have been linked to reduced work efficiency. Addressing the health and welfare of working equids is imperative not only for the animals but also for the households dependent upon them for livelihood. In developing countries, 75 % of working equids have gait or limb abnormalities, but the relationship between workload and prevalence of lameness is unknown. We examined 450 cart mules in Bahir Dar, Ethiopia. Lameness and workload were assessed through use of a survey and lameness exam. We found that 26.8 % of cart mules were lame, and acute lameness of the forelimb was the most common. Animals with poor harness quality were 2.5 times more likely to have sores and 1.6 times more likely to be lame. Lameness tended to be associated with cartloads >700 kg (P = 0.09), and there was a significant association between multiple-leg lameness and cartload weight (P = 0.03). The presence of sores was the best predictor of lameness (P = 0.001). Possible areas of intervention may include education to reduce average daily workload and improving harness design.