Hidradenitis suppurativa (HS) is a painful, inflammatory skin disease associated with a high disease burden and long diagnostic delay. Prevalence estimates of HS vary widely in the literature owing to differing estimation methodologies. This study aimed to apply stepwise algorithms to estimate the prevalence of possible/diagnosed cases of HS in the US. This was a retrospective cohort study in adult and pediatric patients with HS which utilized data from four US databases (MarketScan [Medicare and Medicaid] andOptum [electronichealth record (EHR) andClinformatics Data Mart (CDM)]). Patients withpossible/diagnosed HS were identified using two algorithms (termed Algorithm 1 and Algorithm 2), which assessed symptoms such as multiple skin boils in site-specific areas based on international classification of disease (ICD) codes. Patients with diagnosed HS were defined as having ≥ 2 outpatient or ≥ 1 inpatient diagnosis codes of HS. In each database, patients with continuous medical and pharmacy benefits in the 365days pre-index and 0-365days post-index periods were eligible for inclusion. Across all databases, Algorithm 2 (MarketScan Medicare [N = 309,916]; MarketScan Medicaid [N = 188,783]; Optum EHR [N = 366,158]; Optum CDM [N = 173,812]) identified more patients with possible/diagnosed HS than Algorithm 1 (MarketScan Medicare [N = 194,353]; MarketScan Medicaid [N = 99,276]; Optum EHR [N = 177,957]; Optum CDM [N = 112,244]). Based on ICD-9/10 codes, the 5-year period prevalence of HS ranged from 0.06% to 0.12% across all databases, while for Algorithm 1 and Algorithm 2, this ranged from 0.27% to 0.41% and 0.49% to 0.78%, respectively. Adults and females generally had a higher 5-year period prevalence versus pediatric patients and males, respectively. This real-world study highlights that HS diagnosis codes alone may be insufficient to estimate the prevalence of HS, demonstrating the value of employing algorithms in practice which assess for parameters such as multiple skin boils in site-specific areas. Integrating robust methods to identify the prevalence of HS may improve the diagnostic delay observed in HS and improve treatment outcomes.