The natural circulation loop (NCL) is widely used where the safe and economic heat transfer device is desired. However, the instability associated with the regular change in fluid flow behavior due to the imbalance between friction and buoyant forces is a major disadvantage. One of the erudite solutions to overcome this is to tilt the entire loop by a certain angle, with an inherent penalty in heat transfer and pressure drop. In the present study, experimental studies have been carried out on two-phase carbon dioxide (CO2) based NCL, which has gained popularity because of its compactness and higher heat transfer rate. Pressure drop and heat transfer performance of the loop for various tilt angles (0 deg, 30 deg, and 45 deg) in different planes (XY and YZ planes) have been investigated. Methanol is used as the external fluid in cold and hot heat exchangers in order to maintain low operating temperature in the loop. Results show that the tilting of the loop causes a marginal drop in the heat transfer rate of two-phase CO2 based NCL. Hence, tilting of the loop could be a solution to instability problem without conceding the performance of the loop.