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Abstract Background Half of the adults with current asthma among the US National Health and Nutrition Examination Survey (NHANES) participants could be classified in more than one hypothesis-driven phenotype. A data-driven approach applied to the same subjects may allow a more useful classification compared to the hypothesis-driven one. Aim To compare previously defined hypothesis-driven with newly derived data-driven asthma phenotypes, identified by latent class analysis (LCA), in adults with current asthma from NHANES 2007–2012. Methods Adults (≥ 18 years) with current asthma from the NHANES were included (n = 1059). LCA included variables commonly used to subdivide asthma. LCA models were derived independently according to age groups: < 40 and ≥ 40 years old. Results Two data-driven phenotypes were identified among adults with current asthma, for both age groups. The proportions of the hypothesis-driven phenotypes were similar among the two data-driven phenotypes (p > 0.05). Class A < 40 years (n = 285; 75%) and Class A ≥ 40 years (n = 462; 73%), respectively, were characterized by a predominance of highly symptomatic asthma subjects with poor lung function, compared to Class B < 40 years (n = 94; 25%) and Class B ≥ 40 years (n = 170; 27%). Inflammatory biomarkers, smoking status, presence of obesity and hay fever did not markedly differ between the phenotypes. Conclusion Both data- and hypothesis-driven approaches using clinical and physiological variables commonly used to characterize asthma are suboptimal to identify asthma phenotypes among adults from the general population. Further studies based on more comprehensive disease features are required to identify asthma phenotypes in population-based studies.