Subsea wellhead systems are exposed to wave induced cyclic loading when a drilling unit connects to the well with a marine riser and a BOP. When connected, access is provided to the well and reservoir, and allows for operations such as further drilling, side tracking or workover. Once the operation is completed, the BOP is disconnected from the well, and the wellhead system is not exposed to cyclic loading any longer. Over the lifetime of a well, a number of such operations take place. A wellhead system is perhaps exposed to a total duration of fatigue loading of up to a year, which comprises a sequence of operations of different durations in different seasons. Fatigue predictions for offshore structures are typically based on statistical average of environmental conditions over a large number of years. This is appropriate for permanent installations exposed to continuous wave loading over the lifetime which is often 20 years or more, since variations in the environmental conditions from one year to another is equally represented in the statistics and experienced by the structure. However, for an operation of short duration, the uncertainty in the environmental conditions for that particular period in that particular year needs to be addressed. The weather during October this year is unlikely to be the same as in October last year, and can also be significantly different from average October weather. Although there exists no standard way of doing wellhead fatigue analysis, a commonly applied approach is to do the analysis in a single plane. This is obviously conservative since the wave direction will vary over time, and the fatigue loading will be distributed more around the circumference of the pipe sections in the wellhead system. Furthermore, the environmental conditions are typically based on statistical average for the month or season when the operation is to be executed, sometimes with some conservatism of including the adjacent more severe month or using annual data. Long crested waves are often assumed. This paper address the effect of the uncertainty in the environmental conditions on the accumulated fatigue damage for single and sequences of operations of different durations at different times of the year. A drilling rig in the North Sea has been analyzed using 56 years of hind cast data of significant wave height, peak wave period and main wave direction. Statistics of the fatigue damage rates are calculated and used in a structural reliability analysis in order to estimate reasonably but not overly conservative factors that are to be multiplied with the fatigue damage estimated in a conventional design analyses. Results based on long crested and short crested sea are calculated. An annual variation factor is proposed to account for the variability from one year to another. Secondly, a directional effect factor is proposed to account for the directional variations and its uncertainty on fatigue. Both factors are first estimated considering a single operation only, where the duration is varied between 3 days and up to a year. Thereafter, a sequence of operations of different durations at different times of the year is analyzed, and it is proposed how to consider the accumulated duration of such sequences compared to a single continuous operation. The expected result is an annual variation factor which is greater or equal to unity and a directional effect factor which is less than unity, both with lower values the longer the duration. The product of the two is a quantification of the degree of conservatism associated with a deterministic design analysis using long crested head sea and statistical average omnidirectional weather for the planned drilling operations.