Background: Post-induction hypotension frequently occurs and can lead to adverse outcomes. As target-controlled infusion (TCI) obviates the need to calculate the infusion rate manually and helps safer dosing with prompt titration of the drug using complex pharmacokinetic models, the use of TCI may provide a better hemodynamic profile during anesthesia induction. This study aimed to compare TCI versus manual induction and to determine the hemodynamic risk factors for post-induction hypotension. Methods: A total of 200 ASA grade 1–3 patients, aged 24 to 82 years, were recruited and randomly assigned to the TCI (n = 100) or manual induction groups (n = 100). Hemodynamic parameters were monitored with the pressure-recording analytic method. The propofol dosage was adjusted to keep the Bispectral Index between 40 and 60. Results: Post-induction hypotension was significantly higher in the manual induction group than in the TCI group (34% vs. 13%; p < 0.001, respectively). The propofol induction dose did not differ between the groups (TCI: 155 (135–180) mg; manual: 150 (120–200) mg; p = 0.719), but the induction time was significantly longer in the TCI group (47 (35–60) s vs. 150 (105–220) s; p < 0.001, respectively). In the multivariable Cox regression model, the presence of hypertension, stroke volume index (SVI), cardiac power output (CPO), and anesthesia induction method were found to predict post-induction hypotension (p = 0.032, p = 0.013, p = 0.024, and p = 0.015, respectively). Conclusion: TCI induction with propofol provided better hemodynamic stability than manual induction, and the presence of hypertension, a decrease in the pre-induction SVI, and the CPO could predict post-induction hypotension.