High temperature operation of long wavelength interband cascade infrared photodetectors (ICIPs) has been demonstrated with a working temperature above 300 K. We conducted a comparison study of three sets of ICIP structures, which comprise single absorber barrier detectors and multi-stage ICIPs with four, six and eight discrete absorbers. The 90% cutoff wavelength of these detectors was between 7.5 and 11.5 μm from 78 to 340 K. Advantages of the multi-stage ICIPs over the one-stage devices are demonstrated in terms of lower dark current density, higher detectivity (D*) and higher operating temperatures. Multiple stage ICIPs were able to operate at temperatures up to 340 K with a monotonically increasing bias-independent responsivity up to 280 K, while the one-stage detectors operated at temperatures up to 250 K with the responsivity decreased at 200 K with bias dependence. The D* values for these ICIPs at 200 and 300 K were higher than 1.0×109 and 1.0×108 cmˑHz1/2/W at 8 μm, respectively, which is more than a factor of two higher than the corresponding values for photovoltaic HgCdTe detectors with similar cutoff wavelengths. Interestingly, negative differential conductance (NDC) was observed in these detectors at high temperatures. The underlying physics of the NDC was investigated and correlated with the number of cascade stages and electron barriers. With enhanced electron barriers in the multiple-stage ICIPs, the NDC was reduced, and the device performance, in terms of D*, was improved.