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Quality of life is an important outcome measure in diabetic patients with lower limb amputation (LLA). The aim of this study was to investigate the influence of lower limb amputation on health-related quality of life (HRQOL) in Sudanese diabetic subjects. Additionally the Sense of Coherence scale (SOC-13) and a symptom check list was used in subjects with LLA. A total of 60 (M/F; 40/20) diabetic subjects with LLA and 60 (M/F; 23/37) diabetic reference subjects without LLA, were studied. For both groups HRQOL was measured using The Medical Outcomes Study questionnaire (MOS). Subjects with LLA had significantly poorer HRQOL compared to the reference group in most HRQOL domains (p < 0.0001). Duration of diabetes had the greatest negative impact on HRQOL in both groups, those with LLA (p < 0.0001), and in those without LLA (p < 0.0001), although subjects who were amputated earlier had poorer HRQOL than recently amputated (p < 0.0001). Higher SOC scores were recorded in LLA patients who have greater ratings of positive feelings, family satisfaction and sleep in the HRQOL examination (p < 0.0001). In conclusion, Sudanese diabetic subjects with LLA have a poor quality of life. The triad of diabetes duration, symptoms and amputations, has turned to be important risk factor for poorer HRQOL. Functional and mobility status were suggested to be an important determinant of HRQOL among this population. As the Sudanese population has coherent social relationships, this poor performance of the diabetic subjects will certainly increase the burden on the whole family, in both integrity and economical status. Nevertheless, these deep-rooted social interrelations together with increasing diabetes awareness have substantially improved the family satisfaction among our patients.