This study was conducted to estimate the evolution of antimicrobial susceptibilities of H. pylori strains isolated in Cameroon from 2014 to 2016 in relation to sociodemographic factors and clinical outcomes. A total of 278 H. pylori strains were isolated from patients with gastroduodenal disorders and tested for their susceptibility to nine antibiotics using the disc diffusion method. With time, a significant decreased of resistance was observed against clarithromycin (31.11 to 3.20%, p<0.0001), erythromycin (66.69 to 9.6%, p<0.0001) and metronidazole (86.67 to 69.6%, p<0.0001). Resistance to tetracycline (0 to 2.4%) and doxycycline (0 to 1.6%) slightly increase with time. Resistance to amoxicillin (95.5 to 94.4%), ciprofloxacin (4.44 to 4%) and levofloxacin (0 to 0.8%) was relatively constant. No resistance was detected against rifampicin with the time. A significant decrease of resistance was detected against metronidazole / clarithromycin (22.22 to 1.6%, p<0.0001) and amoxicillin / clarithromycin (26.67 to 3.2%, p<0.0001). Among the tested isolates, 0.92 and 2.4% elicited triple resistance to metronidazole / tetracycline / amoxicillin in 2015 and 2016, and 0.8% quadruple resistance to metronidazole / tetracycline / clarithromycin / amoxicillin in 2016. Higher resistance rate was noticed as age increase and among female compared to men. Our data showed evolution in the antimicrobial susceptibilities of H pylori strains circulating in our milieu with time. This finding highlights the need of monitoring periodically H. pylori resistance profile to antibiotics in order to determine the adapted treatment for this infection.