Helicobacter pylori infection is the etiologic agent of various gastric pathologies. The severity of disease outcome has been attributed to some H. pylori genotypes, which varies geographically. In Morocco, there are no data regarding the pattern of H. pylori genotypes; therefore, this is the first prospective study conducted in our country to investigate the genotype profiles (vacA and cagA) of H. pylori in patients with gastric pain. Endoscopic biopsies were obtained in patients attending the gastroenterology department of the Hospital University Hassan II of Fez for gastric pain and were directly used for H. pylori detection and genotyping by polymerase chain reaction (PCR). The SPSS software program was used to study the genotype correlation to different clinical outcomes. A total of 429 patients were included in this study, with an infection rate of 69.9%. cagA was detected in 42.3% of cases. However, vacA genotyping reveal a large predominance of s2m2. Infection with multiple strains was detected in 10.8% of cases and incomplete vacA was observed in 31.5%. In Morocco, vacA s1m1 was significantly associated to peptic ulcer diseases, while s2m2 was associated to gastritis. Moroccan H. pylori vacA genotype profiles differ from the Latin American, European, and South African profiles, with more similarities to the North African profile. Because of the small number of cases with gastric cancer, no correlations with H. pylori have been studied, so, further studies will be required in order to highlight the effects of those genes on this disease.