A retrospective study of 240 patients aged 12–40 years with moderate to severe acne evaluated the effect of duration of treatment with doxycycline or minocycline (2020–2023) on recurrence and microbial resistance. Patients were divided into three groups: short-term (6–12 weeks, n=80), standard (13–16 weeks, n=80) and extended (17–24 weeks, n=80). Twelve-month recurrence rates increased with length of treatment: 23.8% for short-term, 35.0% for standard, and 46.3% for extended (p < 0.001). Median recurrence-free survival was 9.2 months, 8.1 months, and 6.9 months, respectively (log-rank p < 0.001), with prolonged exposure independently predicting recurrence (adjusted HR: 2.31, 95% CI 1.31–4.07, p=0.004). Short-term treatment success at 12 weeks was similar (73.8–76.3%, p=0.78), scarring (21.3–22.5%, p=0.97) and adverse reactions (27.5–31.3%, p=0.83) did not differ. Resistance to tetracyclines was more common with prolonged exposure (42.9% vs. 13.3–17.6%, p=0.032; n=46). Prolonged antibiotic treatment increases the risk of recurrence without improving short-term results.