Introduction: Spontaneous Breathing Trials (SBTs) are vital in determining readiness for extubation in patients undergoing mechanical ventilation. Pressure Support Ventilation (PSV) and T-piece ventilation are two commonly used methods for conducting SBTs. Aim: To compare the rates of weaning failure, extubation failure, reintubation, and 28-day mortality between patients undergoing SBT using PSV and those using T-piece ventilation. Materials and Methods: A randomised controlled trial with an open-label design was conducted at the Department of General Medicine, PIMS, Pondicherry, Tamil Nadu, india, from from 11 Nov 2019 to 20 Oct 2021. A total of 160 patients requiring mechanical ventilation were randomly allocated into two groups using block randomisation. One group underwent SBT with PSV, while the other group used T-piece ventilation. Ethical approval was obtained, and informed consent was secured from all participants. Primary outcome measures included rates of weaning failure, extubation failure, reintubation, and 28-day mortality. Statistical analysis was conducted using Statistical Package for the Social Sciences (SPSS) version 26, with a p-value below 0.05 considered statistically significant. Results: The study included 64 patients, predominantly male (79.69%) and aged 51-60 years (23.4%), with 45.31% reporting smoking habits and 42.18% consuming alcohol. The mean systolic blood pressure was 130.94 +/- 20.69 mmHg, the mean diastolic blood pressure was 80.00 +/- 12.55 mmHg, and the mean pulse rate was 99.41 +/- 20.78 beats/min. The mean APACHE II score was 16.29 +/- 7.85. The weaning failure rate was 42.9% in the PSV group and 57.1% in the T-piece group, a difference that was not statistically significant (p=0.38). Extubation failure was observed in 14.07% of patients, with no significant difference between groups (p=0.24). Similarly, the reintubation rates (p=0.098) and 28-day mortality rates (p=1.000) were comparable. Conclusion: Both PSV and T-piece ventilation were equally effective for SBTs, with no significant differences in weaning failure, extubation failure, reintubation, or 28-day mortality. The findings suggest that either approach can be utilised effectively based on patient-specific considerations.