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Background: Dyspepsia and headache frequently co-exist, but the clinical implication of this association is uncertain. We planned to examine the prevalence and impact of dyspepsia in adults with headache., Methods: A cross-sectional study was conducted in a secondary care setting. Clinical, psychological and health-related quality of life (HRQOL) data were compared between subjects with headache and controls (non-headache subjects). The impact of dyspepsia was analysed further in subjects with headache alone., Results: 280 subjects (93 cases with headache and 187 matched controls) were recruited. The following baseline characteristics of subjects were as follows: mean age 45.0 ± 17.3 years, 57.0% females and ethnic distribution-Malaysian = 45 (48.4%), Chinese n = 24 (25.8%) and Indians n = 24 (25.8%). Headache sub-types among cases with headache were as follows: tension-type headache (TTH) n = 53 (57.0%) and migraine n = 40 (43.0%). Dyspepsia was more prevalent in cases with headache compared to controls (25.8% vs 12.8%, p = 0.011), and headache was independently associated with dyspepsia (OR 2.75, 95% CI 1.39-5.43). Among cases with headache, there was a trend towards a higher prevalence of dyspepsia in those with migraine (27.5%) compared to TTH (24.5%). Subjects with headache and dyspepsia, compared to those with headache alone, had a greater severity of headache symptoms (63.67 ± 22.85 mm vs 51.20 ± 24.0 mm VAS, p = 0.029). Overall HRQOL scores were lower in headache subjects with dyspepsia (EQ-5D summary score 0.82 ± 0.18 vs 0.90 ± 0.16, p = 0.037 and EQ-5D VAS 62.08 ± 17.50 mm vs 72.62 ± 18.85 mm, p = 0.018), compared to those without dyspepsia., Conclusion: Dyspepsia is associated with more severe headache symptoms and results in a lower HRQOL in patients with headache.