This study assessed the clinical impact of four treatment strategies in adults with type 1 diabetes (T1D): real-time continuous glucose monitoring (rtCGM) with multiple daily insulin injections (rtCGM+MDI), rtCGM with continuous subcutaneous insulin infusion (rtCGM+CSII), self-monitoring of blood glucose with MDI (SMBG+MDI), and SMBG with CSII (SMBG+CSII). This 3-year, nonrandomized, prospective, real-world, clinical trial followed 94 participants with T1D (rtCGM+MDI, n = 22; rtCGM+CSII, n = 26; SMBG+MDI, n = 21; SMBG+CSII, n = 25). The main end points were changes in A1C, time in range (70-180 mg/dL [3.9-10 mmol/L]), time below range (<70 mg/dL [<3.9 mmol/L]), glycemic variability, and incidence of hypoglycemia. At 3 years, the rtCGM groups (rtCGM+MDI and rtCGM+CSII) had significantly lower A1C (7.0% [53 mmol/mol], P = 0.0002, and 6.9% [52 mmol/mol], P < 0.0001, respectively), compared with the SMBG+CSII and SMBG+MDI groups (7.7% [61 mmol/mol], P = 0.3574, and 8.0% [64 mmol/mol], P = 1.000, respectively), with no significant difference between the rtCGM groups. Significant improvements in percentage of time in range were observed in the rtCGM subgroups (rtCGM+MDI, 48.7-69.0%, P < 0.0001; and rtCGM+CSII, 50.9-72.3%, P < 0.0001) and in the SMBG+CSII group (50.6-57.8%, P = 0.0114). Significant reductions in time below range were found only in the rtCGM subgroups (rtCGM+MDI, 9.4-5.5%, P = 0.0387; and rtCGM+CSII, 9.0-5.3%, P = 0.0235). Seven severe hypoglycemia episodes occurred: SMBG groups, n = 5; sensor-augmented insulin regimen groups, n = 2. rtCGM was superior to SMBG in reducing A1C, hypoglycemia, and other end points in individuals with T1D regardless of their insulin delivery method. rtCGM+MDI can be considered an equivalent but lower-cost alternative to sensor-augmented insulin pump therapy and superior to treatment with SMBG+MDI or SMBG+CSII therapy. © 2019 by the American Diabetes Association.