The aim was to evaluate the outcomes associated with four initial management strategies in new patients presenting to primary care physicians with dyspepsia. Patients with new symptoms (no alarm features) were randomised to empirical therapy (n = 11), Helicobacter pylori (HP) serology (n = 8), HP breath testing (n = 11) or oesophagogastroduodenoscopy (n = 13). Dyspepsia and health-related quality of life were assessed using standardised questionnaires at entry, 6 and 24 weeks post-trial enrollment. Outcomes were assessed by structured telephone interview every 6 weeks. In the initial HP testing arms, 21% were positive; 27% in the oesophagogastroduodenoscopy arm had inflammatory changes without ulcers at baseline. The majority (67%) received over the counter medication after initial management. Symptom-free status was similarly common in all groups (p = 0.49); only 20% pursued further evaluation. Total billed charges were higher in the oesophagogastroduodenoscopy group (US 2077 dollars) vs. empirical therapy (US 512 dollars), despite excluding the charge for initial oesophagogastroduodenoscopy, but overall, no effects on total medical charges were detected (p = 0.10). Regardless of initial management, most patients remained symptomatic, yet did not return for health care visits or undergo endoscopies. The cost of upfront endoscopy may not be the best choice for patients presenting with new dyspepsia.