The retrospective study was conducted in tertiary care hospitals between June 2021 and June 2022 to evaluate the risk factors and occurrence of pneumothorax after ultrasound-guided thoracentesis. The study included subjects with pleural effusion in whom pre-procedural thoracentesis under ultrasound guidance was performed. Outcomes were recorded, including chest tube insertion, rate of re-expansion of lungs, length of hospital stay, ICU admission, and mortality rate. Results showed that 500 65 (13%) patients developed pneumothorax. The most frequent etiologies of pleural were congestive heart failure (21%) and malignancy (55%). Multivariate analysis showed an independent association between the volume of pleural fluid drained and the occurrence of thoracentesis-associated pneumothorax (Odds ratio 1.002, 95% Confidence interval 1–1.002; P=.042). It was concluded that pre-procedural thoracentesis under US guidance is associated with a relatively high incidence of pneumothorax. Drainage of a larger volume of pleural fluid is a significant risk factor for developing pneumothorax.