The purpose of this study was to prospectively look for the relative rates and features of musculoskeletal complications in a sample of adult homozygous SS sicklers in Yaoundé. During a 3-year period, known homozygous SS sicklers aged sixteen years or more, with suspicion or evidence of locomotor system disease, including leg ulcer, were consecutively investigated through complete medical history, clinical examination, full blood count, C-reactive protein, standard radiographs of the area of complaint, and, when necessary, CT scan and pus analysis. Those patients with no definite diagnosis were excluded. The study group comprised 84 patients aged 16 to 51 years (mean age: 22 years), with a male/female ratio of 0.75. Four of them (4.5%) were older than 40 years. Thirty five (41.6%) presented a total of 50 lesions of aseptic osteonecrosis, which were located in the hips in 25 cases (50%), in the lumbar spine in 20 cases (40%), in the humeral head in four cases (10%) and in the talar body in one case. The hip necrosis was grade I in 6 cases, grade II in four, grade III in 11 and terminal in four. Multiple sites of necrosis were observed in six patients. Nineteen (22.6%) of the sicklers came on with 36 malleolar ulcers, more frequently in males (sex ratio: 5/1) and 28 (78%) located on the medial side. Fifteen sites of osteomyelitis were noted in 14 patients (17.8%) and septic arthritis in six (7%). Less frequent complications were impingement syndrome, gout osteoarthropathy, stress fracture, subtalar fusion, knee osteoarthritis, tendonitis of the anterior tibialis, and recurrent dislocation of the patella. All patients were managed conventionally, except for advanced aseptic necrosis in which the indication for arthroplasty was delayed till the terminal stage. As suggested by another recent report from Senegal, efforts should be made to improve the life expectancy of sicklers in Sub-Saharan African countries, by acting on education, social and medical care. Orthopaedic surgery should focus on reducing the failure rate of joint replacement in terminal stages of osteonecrosis and designing core decompression trials in early stages.