OBJECTIVE: We sought to examine if 17-alpha-hydroxyprogesterone caproate (170HPC) effectiveness is dependent on the earliest gestational age (GA) at prior spontaneous preterm birth (SPTB) when administered in the clinical setting. STUDY DESIGN: Women enrolled for outpatient services with current singleton gestation and >= 1 prior SPTB between 20-36.9 weeks were identified. Data were divided into 3 groups according to earliest GA of prior SPTB (20-27.9, 28-33.9, and 34-36.9 weeks). We compared GA at delivery of current pregnancy and incidence of recurrent SPTB between women enrolled in outpatient 170HPC administration program (n = 2978) and women receiving other outpatient services without 17OHPC (n = 1260). RESULTS: Rates of recurrent SPTB for those with and without 170HPC prophylaxis, respectively, according to GA at earliest SPTB were: 2027.9 weeks at earliest SPTB, 32.2% vs 40.7%, P = .025; 28-33.9 weeks at earliest SPTB, 34.1% vs 45.5%, P = .001; and 34-36.9 weeks at earliest SPTB, 29.3% vs 38.8%, P = .001. CONCLUSION: 170HPC given to prevent recurrent SPTB is effective regardless of GA at earliest SPTB.