Background: Strongyloidiasis is a parasitic disease with global prevalence. In Spain, autochthonous cases are concentrated in the Mediterranean basin. We aimed to analyze clinical and epidemiological characteristics of Strongyloides stercoralis infection in Vega Baja del Segura (Spain), comparing autochthonous versus imported cases. Methods: Observational retrospective study of all strongyloidiasis cases from January 2009 to January 2019. Cases were diagnosed by stool larvae visualization, positive culture, PCR, Strongyloides serology, and/or compatible histology. Results: We included 36 patients (21 men) with a mean age of 60.8 years ±17.6; 15 cases were autochthonous and 21 imported 80.9% from Latin America. Autochthonous cases were associated with older age (mean 71.3 vs. 53.3 years; p = 0.002), male sex (odds ratio (OR) 5.33; 95% confidence interval (CI) 1.15–24.68; p = 0.041), and agricultural activity (OR 13.5; 95% CI 2.4–73.7; p = 0.002). Fourteen were asymptomatic, three autochthonous cases presented with hyperinfection syndrome, and two patients died. There was no difference between autochthonous versus imported origin in eosinophilia at diagnosis (93.3% vs. 75%; p = 0.207), treatment received, or clinical response (85.7% vs. 88.9% cured; p = 1). Conclusion: In our region, imported strongyloidiasis coexists with autochthonous cases, which are mainly in older male farmers who are diagnosed at more advanced stages. Systematic screening programs are needed.