Introduction: A retrospective cohort study on Salmonella-associated diseases (SADs) was conducted in 14 public hospitals across Lagos State, Nigeria, between 1999 and 2008. Methodology: Medical records of clinically diagnosed patients with confirmed Salmonella infections were reviewed for the 10-year period. Laboratory diagnosis of typhoid fever cases in all the hospitals were first based on Widal agglutination tests then followed by culture, while non-typhoidal Salmonella infections were based on culture technique. Results: A total of 85,187 confirmed cases of SADs were found, of which 880 deaths were recorded (case-fatality rate = 1.03% / 10 years). The mean incidence of SADs in Lagos State for the 10-year period was estimated at 45 cases per 100,000 persons/year, while that of typhoid fever alone was 16 cases per 100,000 persons/year. During the studied period, the number of deaths due to typhoid fever was significantly (P < 0.05) higher than deaths due to gastroenteritis except in 2003 and 2004. Risk associated with typhoidal deaths was 4 to 11 times greater when compared to gastroenteritis deaths between 2000 and 2002. Salmonella-associated diseases were most prevalent in adults 21 -to30 years of age (49.49%). Cases of patients with invasive Salmonella-associated gastroenteritis were observed mainly in children under five years of age. Conclusion: The current surveillance data indicated high incidence of SADs in areas exposed to environmental contaminations. This study revealed that infections caused by Salmonella enterica serovars are endemic in our environment thus poses a serious threat to public health. Constant public health education is essential to avert undue epidemics.