Background and Aims: In Ivoirian's school, the management of vaso-occlusive painful crisis in sickle cell disease requires non steroidal anti inflammatory drugs (NSAIDs). Although their effectiveness, these drugs may be accompanied by intolerance reactions. When these occur, no codified alternative therapeutic seems to be used to our knowledge. Authors aimed to evaluate the induction of tolerance to NSAIDs as an effective alternative therapeutic. Methods: 22 patients (15 men and 7 women aged from 12 to 39 years with mean age: 22.41 ± 7.88) suffering from vaso-occlusive painful crisis were enrolled. They were known to have a history of sickle cell disease and at least one episode of adverse reactions following the Ibuprofen or Diclofenac intake. A rapid protocol of oral challenge was used in patients to induce tolerance to NSAIDs. The first day, initial doses (8.82 mg for Ibuprofen and 2.20 mg for Diclofenac) were given and gradually increased at intervals of 1 hour over a total period of 6 hours. On the second and third days, the therapeutic dose has been orally administrated with an interval of 6 hours over a period of 12 hours. Results: Despite of some cases of failure that might be related to the severity of symptoms or possible patho-physiological mechanism, more than 80% of patients have successfully tolerated Diclofenac and Ibuprofen. Conclusion: This experience appears to be the first in our context. It might be used as a solution in the lack of alternative therapeutic in the management of vaso-occlusive painful crisis of sickle cell disease as well as in other diseases such as HIV infection where patients often develop intolerance to none alternative antibiotics.