The incidence and the risk factors of sickle cell disease (SCD), vaccinated with Pneumococcal vaccine and on penicillin prophylaxis has not been previously reported in India.This prospective hospital based study followed 325 children on penicillin prophylaxis, of which 161 were vaccinated for pneumococci, over 146.84 person years to determine the incidence and determinants of crisis (SCC) and infections. The average age at presentation was 7.05 +/- 3.26 years with male preponderance below 2 years.The main causes for hospitalizations were for blood transfusion, SCC and infections. The incidence of SCC was 1.25 per patient per year and that of infection was 1.38 per person per year. The risk factors for SCC were Mahar caste (p = 0.007) non-compliance (p = 0.000) and protein energy malnutrition (PEM) (p = 0.0015) and for infection were also PEM (p = 0.023), Mahar caste (p = 0.021) and noncompliance (p = 0.001).Malnutrition and non-compliance with medication increased the patient's susceptibility to SCC and infections.