People living in areas endemic for strongyloidiasis are at risk of latent Strongyloides stercoralis infection. Corticosteroid therapy is a well-established risk factor for life-threatening hyperinfection syndrome and disseminated disease owing to suppression of the immune system. There are limited data available on the efficacy and cost of providing oral ivermectin prophylaxis to all patients receiving high-dose corticosteroids for strongyloidiasis in endemic areas. We thus conducted this retrospective cohort study at Khon Kaen University's Srinagarind Hospital from 2015 to 2019. Inclusion criteria were as follows: age ≥ 18 years, having received ≥ 0.5 mg/kg/day of prednisolone or equivalent for at least 14 days, and hospitalization during the study period. A total of 250 patients were included in the study: 125 in the empirical prophylaxis group (prescribed ivermectin even if fecal examination results were negative or nonexistent) and the remaining patients in the definite therapy group (prescribed ivermectin only if S. stercoralis was detected by fecal examination). The prevalence of strongyloidiasis at enrollment estimated by fecal examination was 5.5%. Ivermectin was given to 125 patients (100%) in the prophylaxis group compared with 12 (9.6%) in the definite therapy group (P value < 0.001). During the 12-month follow-up period, S. stercoralis was detected in three patients, two in the prophylaxis group and one in the definite therapy group (P value = 1.000). No cases of hyperinfection syndrome or disseminated disease were found. The empirical prophylaxis strategy had a significantly higher cost than the definite therapy strategy (563 versus 254, P value < 0.001) and did not demonstrate superior efficacy in strongyloidiasis prevention.