The purpose of this cohort study was to determine whether individuals with sickle cell anemia (SCA) were more susceptible to dental caries than non-sickle-cell control subjects. A review of the literature suggests several reasons why individuals with SCA may be at increased risk. Thirty-five cases of SCA aged 6 years and older were identified from a screening of 15,900 current patient files at the Howard University College of Dentistry Dental Clinic. A total of 140 non-SCA control subjects (four per case), frequency-matched on enrollment period (+/- 5 yrs) and age (+/- 2 yrs if under age 21, or +/- 5 yrs if 21 or over), was selected by a nonbiased method from the same dental clinic files. SCA cases and controls were identical on mean age (30.4 +/- 19 yrs, ranging from 5 to 92 yrs) and were similar in sex distribution (males: 34% of SCA cases, 40% of controls). The mean number of permanent teeth present was very similar for SCA cases and controls (23.4 +/- 6.4 vs. 24.2 +/- 6.4). The mean DMFT was 21% higher in the SCA cases (12.0 +/- 8.4 vs. 9.9 +/- 6.9), and the mean DMFS was 26% higher in the SCA cases (33.0 +/- 32.3 vs. 26.2 +/- 27.7). While there was virtually no difference in DMFS between SCA cases and controls for 6- to 19-year-olds, for subjects aged 20 and older, the DMFS was 30.4% higher in the SCD cases. For all ages, the M component for SCA cases was 40.7% higher, and the D component was 20.0% higher, while the F component was only 3.5% higher than for controls. Untreated decay (the D/D+F surfaces ratio) was 24.4% higher in the SCA cases. The findings from this pilot study suggest that SCA cases have a higher susceptibility to dental caries and/or that SCA patients may have different treatment pathways once caries is detected. While none of the observed differences was statistically significant, these findings were of clinical interest and should be pursued in future large-scale studies.