Background: Dyspepsia is the commonest indication for endoscopy. Current American guidelines recommend that all dyspepsia patients ≥ 60 years undergo endoscopy to exclude significant pathology. The use of this age cutoff has never been analysed in South Africa. We aimed to compare different age cutoffs as predictors of significant endoscopic findings in patients with a primary diagnosis of dyspepsia. Methods: A retrospective chart review of 1 000 consecutive endoscopies done at Madadeni Provincial Hospital, KwaZulu-Natal, from 2014 to 2016 was performed. All patients with dyspepsia were identified and divided into age ≥ 60 and < 60 cohorts and < 45 and ≥ 45 cohorts. Demographic data, significant endoscopic findings (tumour, ulcer, and stricture) and non-significant findings (gastritis, hiatus hernia, candidiasis, and oesophagitis, normal) were recorded. Results: 584 patients (58.4%) presented with dyspepsia, with a median age of 49 years (interquartile range: 14-87). There were 142 males (24.4%) and 442 females (75.6%). 432 (74%) patients in the age < 60 cohort and 152 (26%) in the age ≥ 60 cohort. There were 238 (41%) patients in the < 45 cohort and 346 (59%) patients in the ≥ 45 cohort. In the age < 60 cohort, 6.7% of patients had significant findings, compared to 17.1% of patients in the age ≥ 60 cohort (p-value < 0.001). In the age ≥ 60 cohort, the positive predictive value (PPV) of endoscopy was 17%, negative predictive value (NPV) (93%) and odds ratio (OR) (2.87) p < 0.001. In the age < 45 cohort, 4.2% of patients had significant findings, compared to 13% of patients in the ≥ 45 cohort (p-value < 0.001). In the age ≥ 45 cohort, the PPV was 13%, NPV (96%) and OR (3.41) p < 0.001. There is no overall difference in significant endoscopic findings between the age ≥ 45 and age ≥ 60 groups (p = 0.230). Conclusion: Age is a predictor of significant endoscopic findings in dyspepsia patients. Patients ≥ 60 years with dyspepsia symptoms should undergo a routine endoscopy in the absence of alarm symptoms. The current ACG guidelines can be applied in the South African context.