Cobalt-based catalysts have been used to convert H-2 rich syngas derived from natural gas by the Fischer-Tropsch synthesis (FTS). Cobalt-based catalysts exhibit several advantages such as low water gas shift (WGS) activity, favorable C5 + selectivities, and high CO conversion. However, higher conversion achieved in conventional cobalt-based packed bed (PB) reactor often leads to catalyst deactivation due to hot-spot formation, and increased methane selectivity. A conventional cobalt-based PB has low thermal conductivity (0.16 W/m.K), which essentially means poor heat transfer management across the reactor bed. Novel catalyst configuration such as microfibrous entrapped catalyst (MFEC) offers better heat transfer across the bed due to their higher thermal conductivity (9.05 W/m.K). This study reports the performance of FTS over a cobalt-based catalyst in two different types of reactors, the MFEC and the PB utilizing both conventional gas phase (GP) and supercritical fluid (SCF) as reaction media. The focus of the study to investigate the catalyst deactivation mechanism over relatively short time on stream (i.e., 30-40 h). The MFEC bed under the SCF conditions showed very stable performance while both the PB and the MFEC in GP showed steady deactivation profiles. The 1st order steady state activity (a(ss)) for the MFEC-SCF run was determined to be 0.99 compared to MFEC-GP run of 0.83. The a(ss) value for the PB-GP run was 0.61 indicating a higher deactivation compared to MFEC bed run. Chemisorption and TEM imaging revealed a negligible deactivation of MFEC-SCF catalyst as indicated by a slight growth of crystallite size to (similar to)9.5 nm from (similar to)8 nm. SEM imaging and TGA study of the spent catalysts revealed wax deposition being a significant contributor to deactivation in GP-FTS but not in an SCF-FTS. XRD and XPS analysis of the spent catalyst indicated a higher degree of oxidation in GP-FTS as opposed to SCF-FTS.