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Objectives: This study aimed to provide a long-term cost comparison of patients using additional homeopathic treatment (homeopathy group) with patients using usual care (control group) over an observation period of 33 months. Methods: Health claims data from a large statutory health insurance company were analysed from both the societal perspective (primary outcome) and from the statutory health insurance perspective (secondary outcome). To compare costs between patient groups, homeopathy and control patients were matched in a 1:1 ratio using propensity scores. Predictor variables for the propensity scores included health care costs and both medical and demographic variables. Health care costs were analysed using an analysis of covariance, adjusted for baseline costs, between groups both across diagnoses and for specific diagnoses over a period of 33 months. Specific diagnoses included depression, migraine, allergic rhinitis, asthma, atopic dermatitis, and headache. Results: Data from 21,939 patients in the homeopathy group (67.4% females) and 21,861 patients in the control group (67.2% females) were analysed. Health care costs over the 33 months were 12,414 EUR [95% CI 12,022–12,805] in the homeopathy group and 10,428 EUR [95% CI 10,036–10,820] in the control group (p<0.0001). The largest cost differences were attributed to productivity losses (homeopathy: EUR 6,289 [6,118–6,460]; control: EUR 5,498 [5,326–5,670], p<0.0001) and outpatient costs (homeopathy: EUR 1,794 [1,770–1,818]; control: EUR 1,438 [1,414–1,462], p<0.0001). Although the costs of the two groups converged over time, cost differences remained over the full 33 months. For all diagnoses, homeopathy patients generated higher costs than control patients. Conclusion: The analysis showed that even when following-up over 33 months, there were still cost differences between groups, with higher costs in the homeopathy group. [ABSTRACT FROM AUTHOR]