Combinations of analgesics with caffeine have been discussed as bearing a risk for headache chronicity. We investigated whether aspirin with caffeine (ASA+) increases headache frequency compared with aspirin alone in migraine, tension-type headache (TTH), and migraine + TTH (MigTTH). The population-based German Headache Consortium Study, which included participants aged 18 to 65 years, collected information about headache and analgesics at baseline (2003-2007, t0, response rate: 55.2%), first follow-up after 1.87 ± 0.39 years (t1, 37.2%), and second follow-up after 3.26 ± 0.60 years (t2, 38.8%). We included participants with headache at t0, aspirin intake, ASA+ or no analgesics at t0 and t2, and known headache frequency. Linear regression was used to estimate changes of headache frequency (Δt2-t0) and 95% confidence intervals depending on analgesic intake, stratified by headache subtypes, adjusting for sex, age, analgesics at t1, changes of headache frequency at t1, drinking, smoking, body mass index, education, headache frequency at t0. Of 509 participants (56.0% women, 42.0 ± 11.8 years [mean ± SD]), 45.2% reported aspirin intake (41.3 ± 10.9 years, 59.6% women, headache days at t0: 2.8 ± 3.1 d/mo, t2: 3.6 ± 4.1 d/mo), 11.8% ASA+ intake (46.0 ± 9.8 years, 73.3%, t0: 4.8 ± 6.1 d/mo, t2: 5.3 ± 5.1 d/mo), and 43.0% no analgesics (41.6 ± 13.1 years, 47.5%, t0: 3.8 ± 6.2 d/mo, t2: 5.3 ± 6.6 d/mo). There was no increase in headache frequency in participants with ASA+ intake compared with aspirin (adjusted, all headache: -0.34 d/mo [95% confidence intervals: -2.50 to 1.82], migraine: -1.36 d/mo [-4.76 to 2.03], TTH: -0.57 d/mo [-4.97 to 3.84], MigTTH: 2.46 d/mo [-5.19 to 10.10]) or no analgesics (all headache: -2.24 d/mo [-4.54 to 0.07], migraine: -3.77 d/mo [-9.22 to 1.68], TTH: -4.68 d/mo [-9.62 to 0.27]; MigTTH: -3.22 d/mo [-10.16 to 3.71]). In our study, ASA+ intake did not increase headache frequency compared with aspirin or no analgesics.